MDA announces new research grants

Cision published a list of the newest MDA grant recipients today. Click on the link below to read the entire article.

Muscular Dystrophy Association Awards 25 Grants Totaling More Than $6.6 Million for Neuromuscular Disease Research

Critical funding provided by MDA will support studies to further understand disease mechanisms, optimize and build upon existing therapies, and advance drug target identification, especially toward gene-targeted therapies -- research that will have translational and clinical application across many neuromuscular diseases

Spinal-bulbar muscular atrophy (SBMA)

Alireza Mashaghi Tabari, PhD
Leiden University, The Netherlands
Research grant, $300,000
Single molecule folding studies on the mutant androgen receptor underlying SBMA

ALS Disability Insurance Act

ALS Disability Insurance Act of 2019 (H.R. 1407, S.578)

ALS is a quickly progressing disease. People diagnosed with ALS can’t afford to wait to access the SSDI benefits they desperately need.

Currently, all people living with Amyotrophic Lateral Sclerosis (ALS) who qualify for Social Security Disability Insurance (SSDI) must wait five months before they can begin receiving these benefits.

To address this issue and provide relief for these individuals, Sen. Sheldon Whitehouse (D-RI), Sen. Tom Cotton (R-AR), Rep. Seth Moulton (D-MA), and Rep. Peter King (R-NY) introduced the ALS Disability Insurance Act in February 2019. The legislation would eliminate the five month waiting period for SSDI benefits for people living with ALS so that they can begin receiving these benefits immediately.

Because ALS can progress very quickly, it is essential that diagnosed individuals are able to access SSDI benefits as soon as possible. Congress has recognized the urgent need of the ALS community before when it voted in 2000 to waive the two year waiting period for Medicare eligibility for ALS patients.

The Muscular Dystrophy Association has led the way for innovations in ALS science and care for nearly 70 years. We have dedicated hundreds of millions of dollars to ALS research, and care for tens of thousands of people diagnosed with ALS and their families.

MDA Grant for Research on SBMA

The following article appears in NewsWise. Click on the link below to read the entire article.

Dr. Carlo Rinaldi Receives Co-Funded AANEM Foundation/MDA Grant for Research on Spinal and Bulbar Muscular Atrophy

 Carlo Rinaldi, MD, PhD, has been selected as the recipient of a development grant co-funded by the AANEM Foundation and the Muscular Dystrophy Association (MDA). Dr. Rinaldi, who works as an Associate Professor in the Department of Physiology, Anatomy and Genetics in the Division of Medical Sciences at the University of Oxford in the United Kingdom, will be using this funding to increase understanding of the pathophysiology of spinal and bulbar muscular atrophy (SBMA). SBMA is a neuromuscular disorder characterized by the degeneration of lower motor neurons and primary muscle atrophy. Dr. Rinaldi’s ultimate goal is to develop effective therapeutic treatments for this yet incurable condition.

Dr. Rinaldi’s research objective is to characterize the role of the androgen receptor (AR) isoform 2 on AR biology and its impact on SBMA toxicity. His central hypothesis is that AR45 is a key regulator of AR activity and represents a promising therapeutic target for SBMA.

“There is currently no treatment available for SBMA,” explained Dr. Rinaldi. “This research work has the potential to shed new light on the role of the AR isoforms in both health and disease, advance understanding of the mechanisms of pathogenesis in SBMA, and provide a new therapeutic target in close relationship with the disease-causing mutation.” 

“Dr. Rinaldi has the strong support of the Neuroscience community in Oxford to pursue his research into the mechanisms of motor neuron degeneration in SBMA,” noted Kevin Talbot, MB, PhD, FRCP, Head of the Division of Clinical Neurology and Professor of Motor Neuron Biology and Consultant Neurologist at John Radcliffe Hospital in Oxford. “This is a neglected area and he is in an excellent position to be a leader in this field, both within Europe and worldwide.” …

New Funding for SBMA Research

The MDA announced the funding of $9.9 million dollars in research grants. The grant below is for the study of Kennedy's Disease.

Carlo Rinaldi, Ph.D., associate professor and clinician scientist at the University of Oxford in England, was awarded an MDA Development Grant to study how variants in the gene of the androgen receptor (AR) protein cause spinal-bulbar muscular atrophy (SBMA) and investigate whether a novel antisense oligonucleotide therapy approach can target these toxic variants. The results of the study will provide a better understanding of SBMA disease mechanisms, as well as develop a new therapy potentially capable of treating the disease.

This work has potential implications for other diseases of the motor unit as well, including spinal muscular atrophy (SMA) and ALS. This grant is co-funded by the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM).

Additional information was provided on another page:

“Better understanding of the underlying disease mechanisms, coupled with improvement of gene vector design, therapeutic gene selection, and methods of delivery, have made gene therapy a realistic option for neuromuscular conditions — and neurological diseases in general — for which no treatment option was available until few years ago. Many challenges still lie ahead, but we have good reasons to be very optimistic for the future.”

Carlo Rinaldi, associate professor and clinician scientist at the University of Oxford in England, was awarded an MDA Development Grant totaling $120,000 over 3 years to study the role of androgen receptor isoforms in SBMA pathogenesis and the potential as therapeutic targets. This grant is co-funded by the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM).

Mutations in the gene encoding the androgen receptor (AR) protein cause spinal and bulbar muscular atrophy (SBMA). SBMA is an adult-onset neuromuscular condition affecting males with unmet clinical need. It is not undestood how mutations in AR lead to primary degeneration of motor neurons and muscle in patients. The activity of AR and other hormone receptors can be modulated in human cells by isoforms and/or splice variants, which may block or enhance their functions.

Dr. Rinaldi and colleagues plan to investigate the role of AR alternative isoforms in mediating SBMA toxicity. By revealing how these isoforms regulate AR activity in health and disease, researchers expect to better understand the mechanisms of disease in SBMA and provide a novel rational therapeutic target. If successful, the work could pinpoint tissue-specific targets for therapy development, with implications not only for SBMA but for other diseases of the motor unit as well, including spinal muscular atrophy and amyotrophoic lateral sclerosis.

Advice from a 40-year veteran of Kennedy's Disease

Yes, sometimes I am amazed that it has been forty years in the making. I have learned a lot about living with Kennedy's Disease over these last four decades.

A young man stumbled upon my blog the other day and wrote me. He is 34 years old and just diagnosed with Kennedy's Disease. He wrote, "I don’t really know what to expect or even how to deal with things. Can you recommend to me anything as far as exercising or vitamin/ supplements or really anything I can do to try to remain my best possible. My neurologist will only see me every 6 months and really hasn’t told me much other then I need to see a genetic counselor  Any recommendations you may have will be appreciated  "

I responded:.

• Exercise is important. Don't overdue, however. There is something called the 70% rule. Exercise to 70% of your capability. This will keep your good muscles and motor neurons strong and active without doing damage.

• What your weight. As the condition progresses, it becomes more difficult to stay mobile. Keeping your weight down makes it easier to walk and sustain a good level of activity. 

• Exercise and a good diet will go a long way in staying healthy. Inactivity and certain foods contribute to certain health conditions. Since we are less active, we don't burn as many calories and are more susceptible to certain conditions.

• Safety first. When you are young, it shouldn't be too much of an issue, but I did a lot of damage in the early years because I didn't know when to back off.

• Keep a positive mental attitude. 

• Life doesn't end with KD; it just changes. If there is something positive about KD, it is the slow progression of the condition. You shouldn't observe too many problems in the early years. 

• Seek out support from those of us living with KD. The KDA, the KDA Forum, Facebook, etc. Always remember you are not alone.

• Most importantly, KD does not define who you are and what you are capable of doing. Observe, adjust and stay active. You might not physically be able to accomplish something the way you used to do it, but it can still be done or you can ask someone to do it for you.

What I thought of later:

• Dr. Grunseich at the NIH recommended the following. Those of us living with Kennedy’s Disease should avoid high doses of B-6 because it worsens the neuropathy systems. The normal dosage in a multi-vitamin should be fine.

• He also said that we should consider taking additional supplements of B-12 because it is good for the nervous system.

• Swallow your pride. It is okay to ask for help when you need it. Others will understand and look forward to helping. 

• The MDA Clinics are beneficial for those of us living with progressive conditions. There are clinics in most major cities in the U.S. and Canada. I am certain there are similar organizations in other countries. Join one of these groups. They provide excellent support and give you access to certain mobility aids through their "Loan Locker."

• At some point when mobility has become an issue, consider taking Dutasteride. I feel it has helped me maintain my strength.

MDA Announces SBMA Research Grant

This week the MDA announced the awarding of more research grants. Of particular interest to those of us living with Kennedy’s Disease (SBMA) is the following grant.

Testing a potential therapy for spinal-bulbarmuscular atrophy (SBMA)

“Scientists at the University of Michigan Medical School in Ann Arbor are completing preclinical studies in a mouse model to establish the safety and efficacy of a new type of therapy to silence activity of the gene that is mutated in SBMA.”

Below is the abstract of the research noted in the above announcement. It should be noted that Dr. Lieberman serves on the Kennedy’s Disease Association’s Scientific Review Board.

Rescue of MetabolicAlterations in AR113Q Skeletal Muscle by Peripheral Androgen Receptor GeneSilencing

Giorgetti E1, Yu Z1, Chua JP1, Shimamura R1, Zhao L2, Zhu F3, Venneti S1, Pennuto M4, Guan Y3, Hung G5, Lieberman AP6.

Abstract

“Spinal and bulbar muscular atrophy (SBMA), a progressive degenerative disorder, is caused by a CAG/glutamine expansion in the androgen receptor (polyQ AR). Recent studies demonstrate that skeletal muscle is an important site of toxicity that contributes to the SBMA phenotype. Here, we sought to identify critical pathways altered in muscle that underlie disease manifestations in AR113Q mice. This led to the unanticipated identification of gene expression changes affecting regulators of carbohydrate metabolism, similar to those triggered by denervation. AR113Q muscle exhibits diminished glycolysis, altered mitochondria, and an impaired response to exercise. Strikingly, the expression of genes regulating muscle energy metabolism is rescued following peripheral polyQ AR gene silencing by antisense oligonucleotides (ASO), a therapeutic strategy that alleviates disease. Our data establish the occurrence of a metabolic imbalance in SBMA muscle triggered by peripheral expression of the polyQ AR and indicate that alterations in energy utilization contribute to non-neuronal disease manifestations.”

Accessible Air Travel; Let members of Congress know it's important

Back in May I posted an article on Accessible Air Travel and what is being done to improve our travel experiences.

The MDA Advocacy Group has posted the following message asking for everyone's support to help push this through..

Take Action for Accessible Air Travel

Thank you to everyone who has joined us in advocating for increased access to air travel.  Many of you contacted your Senators previously, encouraging them to include provisions to increase air travel accessibility in the FAA reauthorization.  All four of those provisions were included in the final version that passed the Senate by an overwhelming vote of 95-3, thanks in part to the actions of many advocates.  

As you will recall, the accessible travel provisions in the Senate bill call for:
1) studying the use of in-cabin wheelchair restraint systems, 
2) identifying best practices in airport accessibility, 
3) examining training policies regarding assistance for disabled air travelers and 
4) creating an advisory committee with diverse stakeholders to investigate and report to Congress on the needs of passengers with disabilities. 

The same provisions that would increase access to air travel for passengers with disabilities, however, are not included in the current version of the FAA reauthorization in the House of Representatives.  The House and Senate are now considering how to move forward and an extension may be the first step.

Please TAKE ACTION TODAY to let your members of Congress know that accessible travel provisions are important to passengers with disabilities, and that as they work out an agreement, we urge them to include the provisions in any final FAA reauthorization or in any action that would extend the FAA’s current operating authority.

If you would like to help by contacting your representatives, please follow this link:  TAKE ACTION NOW

Accessible Air Travel

For those of us living with a progressive disorder, accessible air travel becomes more of an issue over time. My last job required quite a bit of travel in the United States and Canada. Long lines, the distance to the gates, waiting, changing planes, more long lines, the distance to baggage claim—I think you get the point—had me worn out even before I even visited out customers, warehouses and mills. And, I'm not going to even mention the plane's tight seating, and bathrooms.

Once I had a nasty fall while exiting a plane. More than once I fell because of fatigue after arriving at the destination. In short, airlines are really not set up to accommodate those of requiring special needs when traveling.  

The update below from the MDA shows that some progress is being made in this area.

Accessible Air Travel Update

MDA has been working closely with a diverse set of stakeholders that include policy makers, advocate groups, industry and MDA families to support increased accessibility to air travel.  Thank you to everyone who contacted your U.S. Senators to urge their support for the disabled passengers provisions contained in the Senate version of the FAA reauthorization bill.  These provisions would call for 1) studying the use of in-cabin wheelchair restraint systems, 2) identifying best practices in airport accessibility, 3) examining training policies regarding assistance for disabled air travelers and 4) creating an advisory committee with diverse stakeholders to investigate and report to Congress on the needs of passengers with disabilities.

The bill passed the full Senate with overwhelming support (vote 95 to 3) - with allfour of the disability provisions intact.  Two amendments pertaining to enforcement of the Air Carrier Access Act were offered, but were not included in the final version of the legislation.

The next step is for the U.S. House to take action.  We will follow up with additional information on how you can take action as the legislative process moves forward.  Additionally, the Department of Transportation (DOT) recently convened the first meeting of the Accessible Air Transportation Advisory Committee (ACCESS) in Washington, D.C. to address three issues impacting accessibility: 1) lavatories, 2) service animals and 3) in-flight entertainment.  The committee will consider all three issues in the coming months, and we will provide updates and summaries about this effort as it progresses.  If you are interested in learning more about the accessible air travel initiative or are planning air travel in the near future, check out MDA'sAccessible Travel Resource Center.

Photo: Coastal Air Tours

Diane Merry - SBMA Researher

The MDA published the following article on a Kennedy's Disease researcher many of us know.

Five Questions with SBMA Researcher Diane Merry

Diane Merry, associate professor at Thomas Jefferson University in Philadelphia, is working to identify therapeutic opportunities to promote normal androgen receptor function while preventing the toxic effects of polyglutamine expansion in spinal-bulbar muscular atrophy (SBMA). With GlaxoSmithKline, Merry will test small molecule compounds that activate an enzyme called SIRT1 in cell and mouse models of SBMA to determine their therapeutic potential.

Please describe your current research in SBMA.
Many neurodegenerative diseases result from protein misfolding and accumulation due to genetic or environmental causes. SBMA is one such disease; it is an inherited, adult-onset, neuromuscular disease that is caused by the expansion of a polyglutamine tract within the androgen receptor (AR) and is related mechanistically to other neurodegenerative diseases caused by polyglutamine expansion.

An important feature of SBMA is that its onset and progression are dependent on the binding of androgenic hormones to the mutant receptor. Our studies of mouse and cell models of SBMA that reproduce the androgen- and polyglutamine-dependent nuclear AR aggregation seen in patients, as well as its toxicity, revealed that the mutant AR must be modified by the addition of acetyl groups for its aggregation and toxicity. Moreover, the deacetylase SIRT1 is strongly neuroprotective in cell models of SBMA and this neuroprotection largely depends upon its ability to remove acetyl groups from the mutant AR.

We are investigating the therapeutic potential of activating this acetyl group-removing enzyme, SIRT1, with small molecule activators. We will test these compounds in cell models, and ultimately in mouse models, of SBMA.  We anticipate that these studies will reveal new and powerful opportunities for therapeutic development in SBMA.

Is this your first MDA grant?
No, I was funded previously (as a post-doctoral fellow and then when I started my lab) by MDA.  It means a tremendous amount to me to be funded once again by this organization that is so committed to finding a cure for neuromuscular diseases.

What inspired you to study SBMA?
I come from a strong background of training in molecular genetics and molecular pathophysiology. I began to study the molecular basis of this disease in 1993, just a short time after the genetic cause of the disease was identified.  I have been studying SBMA ever since that time — for the past 22 years.

What is your focus within the SBMA field, and why is it important?
My focus is on the mutant androgen receptor protein itself and the effect of the polyglutamine expansion on androgen receptor metabolism (structure, trafficking, protein interactions, turnover), in order to identify therapeutic opportunities to promote normal androgen receptor function while preventing the toxic effects of the polyglutamine expansion. The work funded by this grant is designed to do just that.

There is currently no effective therapy or cure for SBMA and thus an effective therapy is a primary goal of our work. The work funded here is likely to bring us closer to that goal.

What do you feel people impacted by SBMA can have the most hope about with respect to research right now?
We know so much more about the disease process at this point in time, and we and others have identified disease targets for therapeutic development. I do think that a therapy or therapies are within sight for SBMA in the foreseeable future.

Does your work have any potential implications for other disease fields?
Our work has implications for other diseases in which the enzyme SIRT1 is neuroprotective.  Although the SIRT1 target proteins may be distinct, the identification of small molecule activators of SIRT1 is likely to open up possibilities for using these activators to treat other diseases.

For your consideration

The MDA sent out an email yesterday concerning a proposed change that would cut payments for more complex wheelchair accessories. This is something that needs our, those of us living with Kennedy's Disease, attention.

As some of you might know, seats that elevate are not covered by Medicare. This has always been frustrating. With a lift seat, I can still transfer to another chair, the toilet, and the bed. Without it, I would need to have someone capable of assisting me by my side all day.With adjustable seats, seat backs, and leg rests, I can take pressure off of my hips, buttocks. legs, etc.

Please read the bulletin below and consider contacting your representative by clicking on the link below. Thank you.

Help Preserve Access to Complex Rehab Technologies By Taking Action Today

The Medicare program is planning to cut payments for complex rehab wheelchair accessories that are needed by people living with muscular dystrophy, ALS, Spinal Muscular Atrophy (SMA) and other neuromuscular diseases.   The cuts are set to take effect on January 1, 2016 and would limit access to critical accessories such as custom head support and seating systems, mounting hardware, adjustable leg rests, and specialty drive controls among other wheelchair accessories that people living with these diseases rely on each day of their lives.  Therefore, we need your help today!

The Muscular Dystrophy Association (MDA) and ALS Association have joined together to support legislation introduced in the House (H.R. 3229) and Senate (S. 2196) that would stop these cuts and ensure that people with muscular dystrophy, ALS and other neuromuscular diseases continue to have access to the full range of complex rehab accessories that meet their medical needs.

Please contact your members of Congress and urge them to cosponsor this critical legislation. Because the bills must be passed and enacted by December, 31, 2015 in order to prevent these cuts, it is critical that you contact Congress today!  A letter you can customize and email directly to your elected officials is available by clicking here. 

Background:   
In 2008, the Muscular Dystrophy Association (MDA) and the ALS Association supported legislation that specifically excluded complex power wheelchairs and related accessories from Medicare’s competitive bidding program.  Congress took this action because they understood that the competitive bidding program did not recognize the complexities of neuromuscular diseases like ALS and muscular dystrophy, the difficulties imposed by the diseases, or the sophisticated equipment and services that are required to help improve the lives of people living with these diseases.  Since that time, complex rehab accessories have not been included in the competitive bidding program.   However, Medicare is now planning to change that, despite existing law that specifically excludes these technologies and despite the fact that such a change could reduce or even eliminate the availability of these vital technologies.

H.R. 3229 and S. 2196 would make technical corrections to the law to clarify that complex rehab wheelchair accessories should continue to be covered using Medicare’s established fee schedule amounts and not be paid for using competitive bidding prices, which do not capture the full cost of these customized accessories.  The bills follow the intent of Congress with passage of section 154 of the Medicare Improvements for Patients and Providers Act (MIPPA) in 2008 and would help to ensure that complex rehab technologies remain available to people with ALS and muscular dystrophy, and other neuromuscular diseases.

ADA Turns 25

The MDA Advocacy News sent out the following:

As the ADA turns 25...

On July 26, 1990, the Americans with Disabilities Act (ADA) was signed into law, marking an important step forward for individuals with disabilities and their families.  The legislation elevated the importance of equal access for children and adults with disabilities and engaged the country in a conversation about the inherent rights every person has, regardless of ability.  The ADA changed the landscape for people with disabilities—it is the primary reason we have accessible parking spaces and building entrances and why those of us with limited mobility can navigate school campuses and access and enjoy public libraries, retail stores, movie theaters and doctors' offices. 

As the ADA turns 25, we come together to celebrate the accomplishments of this legislation while maintaining our focus on continued, collective efforts to protect and enhance the rights of our disability community, where there is still much work to be done.

_________________________________

Being an 'old-timer', I find it difficult to believe that it was only 25 years ago that things started to change for those living with a disability. I still become frustrated when I do not have access to certain buildings or a handicap bathroom is nothing more than two grab bars attached to a normal toilet. Yet, I am thankful for all the changes that have been made to allow me access to facilities including designated parking areas. Probably the biggest change is the mindset of the majority of people. Thank you ADA.

For more information on the ADA, visit:  http://www.ada.gov/

Ensuring Access to Clinical Trials

The MDA sent out the following update this morning.

July 17, 2015

Legislation Ensuring Access to Clinical Trials for People with Neuromuscular Diseases Passes U.S. Senate

On July 16, 2015, the U.S. Senate passed the Ensuring Access to Clinical Trials Act (S.139), which removes barriers for those with neuromuscular and other rare diseases to participate in clinical trials.

The bipartisan legislation makes permanent the Improving Access to Clinical Trials Act of 2009 ("IACT") that is scheduled to expire in October 2015. The bill stipulates that up to $2,000 of compensation will not be counted as income toward patients' eligibility for Supplemental Security Income (SSI) or Medicaid. By making the IACT permanent, those with muscular dystrophy, Amyotrophic Lateral Sclerosis (ALS), Spinal Muscular Atrophy (SMA) and other neuromuscular and rare diseases will be able to continue to participate in clinical trials without the risk of losing vital benefits.

MDA is proud to partner with the Cystic Fibrosis Foundation, the National Organization for Rare Disorders, and more than seventy other groups- who together represent millions of individuals-in support of the Ensuring Access to Clinical Trials Act of 2015 ("EACT") (S.139/H.R.209).

An identical bill is currently pending in the U.S. House of Representatives (H.R. 209). Please click the button below to receive advocacy alerts and updates about this and other important policy initiatives.

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It is good to hear that more than 70 organizations have come together to support the passage of this Act.  Additional information and details about the act can be found at Congress.Gov .

21st Century Cures Act Passes

Back in May I asked you to show your support for the National Institutes of Health by contacting your representatives. I felt this was important for any of us living with a neuromuscular disease or any other rare disorder including Kennedy's Disease (SBMA).

Good news!  The funding bill passed; Below is the message sent out from the MDA today. Thanks to all of you who took the time to show your support for the 21st Century Cures Act.

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21st Century Cures Act Passes with Overwhelming Support

Today the U.S. House of Representatives overwhelmingly passed the bipartisan 21st Century Cures Act by a vote of 344-77. The Act includes important provisions aimed to accelerate the discovery, development and delivery of treatments and cures, including increased funding for the National Institutes of Health (NIH).

Increased support for NIH is critical, as funding levels have failed to keep up with the rising costs of medical research. This has resulted in a 22% decrease in the purchasing power of the NIH and in fewer research grants being funded. The 21st Century Cures Act makes important strides to remedy this by authorizing increased NIH funding levels and creating a NIH Innovation Fund that provides an additional $8.75 billion to the NIH over the next five years.

Show your support for NIH

MDA's Outreach Program sent out a message this week that needs to be passed along and supported by all those living with a neuromuscular disease (ALS, SBMA, SMA, etc.).

As many of you know, NIH is currently conducting a clinical trial for a treatment for Kennedy's Disease. If this phase goes well and the treatment is determined to be safe, NIH will move to the next phase and open the trial up to a larger group of patients.

Read the message from the MDA below and consider supporting the proposed increase to NIH spending.

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Increase Funding for the National Institutes of Health (NIH)

Increased funding for the National Institutes of Health (NIH) is critical to finding treatments and cures for the neuromuscular diseases that affect our community. Together, with our generous donors and sponsors, MDA is working to fund groundbreaking research and bring critical support to families. Collaboration-including leveraging federal funding-is vital to speed urgently needed treatments to affected individuals as quickly as possible.

Ensuring increased NIH funding is one of MDA's top policy priorities. Through targeted efforts and strategic initiatives, MDA is urging Congress to boost funding for NIH. Increased support for NIH is critical, as funding levels have failed to keep up with the rising costs of medical research-resulting in a 22% decrease in purchasing power since 2003, when adjusted for inflation. This lack of funding has resulted in a lower grant application success rate and hinders the ability of NIH to conduct and support important biomedical research.

With many voices carrying the message that medical research is imperative to finding treatments and cures, lawmakers have placed increased NIH funding on the Congressional agenda in both the Senate and the House of Representatives.

One example is the 21st Century Cures Act draft released May 13, 2015, by the House Energy &

Commerce Committee. This draft would authorize an increase in NIH funding and would create an NIH Innovation Fund that would increase NIH funding by $10 billion over five years. MDA applauds the bipartisan efforts of the Energy & Commerce Committee for making NIH funding a priority and appreciates the efforts of Chairman Fred Upton (R-MI-06), and Rep. Diana DeGette (D-CO-01), Frank Pallone (D-NJ-06), Joe Pitts (R-PA-16) and Gene Green (D-TX-29) to ensure that increased NIH funding is included in the draft legislation.

In addition to the 21st Century Cures Act, several pieces of stand-alone legislation in the House and Senate support increased NIH funding at various levels. MDA appreciates the efforts of every lawmaker who takes action to increase funding for medical research.

Please click the button below to urge your Congressional leaders to support increased NIH funding. 

Government Funding for NMD Research

Below is an article from the MDA’s Quest Magazine on government funding for neuromuscular disease research for 2013. 

Government Funding for NMD Research Largely Spared in Continuing Resolution

The congressional funding bill spared government programs that sponsor neuromuscular research, but it doesn't protect them from upcoming deep sequester cuts.
Article Highlights:

• Government programs that fund neuromuscular disease research fared well in the recent continuing resolution passed by Congress on March 21. The continuing resolution funds the government through the end of September 2013.
• Neuromuscular disease research is sponsored by several government agencies, including the National Institutes of Health, U.S. Food and Drug Administration, Centers for Disease Control and Prevention, and Department of Defense.
• The continuing resolution does not avert pending cuts caused by the sequester. MDA’s advocacy program “will continue to work to ensure that congressional appropriators understand the importance of this life-altering work … as decisions are being made about funding for fiscal year 2014.”

by Quest Staff on March 25, 2013 - 12:27pm

The news is generally favorable for many important government-funded neuromuscular disease research projects, in the wake of Congress’ recent passage of a continuing resolution funding the government through the end of September.

Most government operations, except those funded through the full-year appropriations bills, will be maintained at essentially the same level as fiscal year (FY) 2012. (The government's fiscal year begins on Oct. 1 and ends on Sept. 30 of the following year.)

Neuromuscular disease research projects are spread across several governmental agencies, including the National Institutes of Health (NIH); the Food and Drug Administration (FDA); the Centers for Disease Control and Prevention (CDC); and the Department of Defense (DOD).

• NIH and FDA: Both agencies received slight funding increases in the continuing resolution bill. These agencies fund basic, clinical and translational research into neuromuscular disease, as well as oversee the approval of new drugs, biologic products and medical devices.
• CDC: The funding bill maintained last year’s funding level for the CDC. This agency implements the muscular dystrophy program through the CDC National Center on Birth Defects and Developmental Disability (NCBDD), established by the MD CARE Act and the National ALS Registry at the CDC Agency for Toxic Substances and Disease Registries (ATSDR), established by the ALS Registry Act.
• DOD: One of the full-year appropriations bills to be included in the continuing resolution was funding for the DOD. Congress directed that FY2013 funding for amyotrophic lateral sclerosis (ALS) research be slightly increased and that funding be maintained at its current level for Duchenne muscular dystrophy (DMD). In fiscal year 2012, DOD funding for ALS research was $6.4 million, which will increase to $7.5 million in FY2013, and DMD funding held steady at $3.2 million.

“MDA is pleased that this congressional funding bill will continue to allow for the progression of vital research and critical therapy development,” said Annie Kennedy, MDA senior vice president for advocacy.

"Halting our discovery momentum at such a promising time by reducing federal scientific funding would be a ‘worst-case’ scenario. And since that potential still exists, we are continuing to work to ensure that congressional appropriators understand the importance of the life-altering work being funded by the NIH, FDA, CDC and DOD as decisions are being made about funding for fiscal year 2014.”

Kennedy noted that the continuing resolution does not avert the pending deep federal budget cuts known as the "sequester," although it does give more leeway to agencies in deciding how to make those cuts.

MDA is working with Representatives Ed Markey (D-Mass.) and David McKinley (R-W.Va.), and a coalition of national patient advocacy organizations to convince Congress to give full funding to medical research in the next fiscal year.

“Raise your voice,” urged Kennedy. “Tell Congress to provide full funding to vitally important research in 2014!”

Slowing Kennedy’s Disease Progression

MDA’s Quest Magazine published an interesting article reported by Amy Madsen on some recent research by a member of the Kennedy’s Disease Association’s Scientific Review Board. Dr. La Spada has been instrumental in Kennedy’s Disease research for many years.

While the research opportunity still needs further study and testing, preliminary findings reflect this could be a potential treatment.

Below is the Quest article.

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Arimoclomol Slows Disease Progression

in SBMA Mice

Mice treated with the small-molecule compound improved muscle strength, increased motor neuron survival and boosted production of a motor-neuron support molecule called VEGF


MDA research grantee Albert La Spada and colleagues have found that treatment with a compound called arimoclomol can help improve muscle function in mice with a disease resembling SBMA.

Article Highlights:

• An MDA-supported research team has shown that treatment with a small-molecule compound called arimoclomol improved nerve-cell survival, resulting in increased muscle strength and function in mice with a disease resembling spinal-bulbar muscular atrophy (SBMA).
• Arimoclomol is thought to work by inducing the heat shock response, which helps cells combat exposure to heat or other types of stress. 
• Although still early stage, the findings ultimately could lead to development of arimoclomol or similar compounds as a treatment for SBMA.

by Amy Madsen on March 4, 2013

Mice with a disorder mimicking human spinal-bulbar muscular atrophy (SBMA, or Kennedy disease) that were treated with an experimental therapy called arimoclomol showed improved nerve-cell survival, increased body weight, and better muscle strength and function than mice that didn't receive the treatment.

A small-molecule compound, arimoclomol is thought to work by inducing the heat shock response, in which levels of naturally occurring heat shock proteins (HSPs) increase when cells are exposed to heat or other types of stress.

The findings, which could lead to development of arimoclomol or similar compounds as a treatment for SBMA, were reported online Feb. 7, 2013, in Brain. MDA supported Albert La Spada at the University of California, San Diego, in La Jolla for his contribution to this work. (To read the full report, available for a fee, see Co-Induction of the Heat Shock Response Ameliorates Disease Progression in a Mouse Model of Human Spinal and Bulbar Muscular Atrophy: Implications for Therapy.)

Treatment began after symptom onset
Mice in the study were randomly assigned to two different groups, in which they were treated with 120 milligrams per kilogram of body weight per day of arimoclomol dissolved in drinking water (treatment group) or water alone (control group). Treatment began at 12 months of age, after symptom onset and lasted for six months through late-stage disease.

Results show that treatment with arimoclomol from the time of symptom onset dramatically delayed disease progression. When investigators examined 18-month-old SBMA mice, they found that those treated with arimoclomol:

• demonstrated significantly improved hind-limb muscle force;
• had 26.9 percent stronger muscles than did untreated mice;
• showed a 23-percent improvement in motor unit (a nerve cell and the muscle fibers it activates);
• had significantly increased muscle weight; and
• had a 28.4-percent increase over untreated mice in the number of motor neurons that survived.

Mice treated with arimoclomol also had higher levels of a protein called vascular endothelial growth factor (VEGF), a protein that may protect or nourish nerve cells.

Treatment with arimoclomol had no effect on muscle force in mice that didn't have an SBMA-like disorder. This, the investigators noted, suggests that beneficial effects of arimoclomol in the mice are likely due to specific effects of the drug on disease processes, as opposed to indiscriminate improvement of muscle force.

Arimoclomol activated the heat shock response
Several treatment strategies for SBMA have focused on inducing overexpression of heat shock proteins, such as HSP70 and HSP90. (HSPs can function as “chaperones” for other proteins, helping them fold into the right shape, preventing them from forming abnormal clumps and blocking cell death.)

Data from the current study showed that levels of heat shock protein 70 (HSP70) were 2.3 times higher in the spinal cord and three times higher in hind-limb muscles in mice treated with arimoclomol than in mice that didn't receive treatment. 

This upregulation (increase) of the heat shock response by treatment with arimoclomol may have therapeutic potential in the treatment of SBMA, the researchers say.

IGF-1 Continues to Show Promise

GOOD NEWS on the Research Front

 

MDA’s Quest Magazine just published an update on IGF-1. Maria Pennuto, a previous recipient of a KDA Research Grant and MDA funding, provided the following update to reporter Amy Madsen.

I have written about IGF-1 in several previous posts because of its potential. We hope to hear more promising news at the upcoming KDA Conference and Educational Symposium the second week of October in New Orleans.

______________________ 

SUMMARY

• Mice with a disease resembling spinal-bulbar muscular atrophy (SBMA) that were treated with an insulin-like growth factor 1-based compound had better motor function, slower weight loss, improved muscle health and increased survival time.
• Recent studies have shown that IGF1 works in SBMA by reducing toxicity caused by a mutation in the androgen receptor (AR) gene; it also helps promote muscle and nerve growth.
• The new findings suggest that IGF1 potentially may be effective in ameliorating the disease.

Mice with a disease resembling spinal-bulbar muscular atrophy (SBMA, or Kennedy’s disease) that were treated with a compound based on insulin-like growth factor 1 (IGF1) had better motor function, slower weight loss, healthier muscles and longer survival time than mice that received an inactive substance, an MDA-supported research team has reported.

The research team also found that SBMA mice that overproduce a muscle-specific form of IGF1 have a milder disease course than mice that produce less of the protein.

The new findings suggest that IGF1 potentially may be effective in ameliorating the disease via at least two mechanisms:

• directly reducing toxicity caused by a mutation in the androgen receptor (AR) gene by changing the way the androgen receptor protein behaves; and
• generally promoting and regulating skeletal muscle growth, and improving survival of muscle-controlling nerve cells called motor neurons.

The research team reported its findings online Aug. 29, 2012, in Molecular Medicine. To read the full report, see IGF-1 Administration Ameliorates Disease Manifestations in a Mouse Model of Spinal and Bulbar Muscular Atrophy. MDA supported Maria Pennuto at the Italian Institute of Technology in Genoa, Italy.

Findings show IGF1 compounds hold therapeutic potential
 
The researchers treated SBMA mice with a compound called mecasermin rinfabate (brand name Iplex), which is a combination of IGF1 and IGF1 binding protein 3. (The binding protein helps IGF1 last longer in the body.)

Male mice were randomly assigned to receive abdominal injections of the IGF1-based compound at a daily dose of 15 milligrams per kilogram of body weight, or an inactive substance. To mimic the typical clinical setting (in which a diagnosis of SBMA occurs after symptoms appear) the researchers began injections when the mice were 10 weeks old, after disease onset, and continued through 20 weeks.

The researchers evaluated body weight, motor function and survival in the mice. They found that, when compared to the placebo-treated mice, those treated with IGF1 had:

• less body weight loss;
• significantly improved grip strength; and
• longer survival time (by an average of approximately three weeks).

In addition, the researchers found that the IGF1-treated mice had markedly reduced muscle shrinkage (atrophy) and degeneration.

The study results provide a basis for further study of IGF1-based compounds as potential therapies for people with SBMA.

Preparing for Emergencies

MDA’s Health Care Services had an interesting article on emergency preparedness that everyone should read whether disabled or not. Several of the links mentioned in the article are shown below.

The federal government has a website with additional information on different types of emergencies and services available for your area. The link to the website is: Disability.gov's Emergency Preparedness Section.
 
The MDA has put together a good checklist for people who have neuromuscular diseases. Not every item applies to those of us living with Kennedy’s Disease, but many apply to anyone with special needs or considerations. The checklist can be downloaded (PDF) at this link: PDF Checklist.
 
Another good link to always have bookmarked is the National Weather Service.  You can zoom in on your area and receive the most current updates and forecasts along with other helpful information.

If you must evacuate your residence and need MDA services, or information about local groups offering emergency assistance, you can reach the MDA by calling (800) 572-1717 or emailing healthcareservices@mdausa.org. They will connect you to the MDA office serving the area in which you've sought shelter.

As the Boy Scouts always say, BE PREPARED.