Disability; How to Apply for

Notes:
1. Even though the process will be different in other countries, I believe the principles and suggestions will apply to any process.]
2. This is a long article. Consider printing it and filing it with other related information.

Depending upon the type of work you do, at some point you might need to consider retiring because of safety issues and/or inability to perform your assigned tasks.

Social Security – Disability (SS-D) is important to many of us in the United States who are forced to retire early because of health related issues. A few years ago, I wrote a 'guide' for applying for SS-D based upon my experience. Since the guide is twenty pages long, in this post I will try to focus on the ‘key learnings' that might make the process easier for you if you ever need to apply. There is a link to the PDF guide at the bottom of this article.

How SS-D works: It is important that you understand how Social Security defines 'disability'. That is because other programs have different definitions for disability. Some programs pay for partial disability or for short-term disability. Social Security does not. Disability under Social Security is based on your inability to work. You will be considered disabled if you cannot do work you did before and they decide that you cannot adjust to other work because of your medical condition(s). Your disability also must last or be expected to last for at least a year or will result in death.

• Note: Progressive disorders are different and this is why you need to work with your doctor and your Social Security representative in order to explain the gradual and continual loss of certain functions. 

Here is how to make the process work for you

I know you can apply on-line, but I do not recommend it. You have a story to tell and someone needs to hear it. For my reasoning, see “Educate the Reviewer” and “Tell your Story” below. You do not want to be a name on a form. You want someone to associate your face, personality, and capabilities with your condition.

A doctor who reviewed disability claims for a Fortune 100 company gave me the following advice on the disability application process.

Start the process early. Do not wait until you are totally disabled before beginning the process.

Be patient. The process takes time. It is not uncommon to wait 90-120 days before hearing the results of the application.

Fill out the forms completely. The disability process is no different from any other application process (e.g., home loan, employment, etc.). Provide explanations for terms used. Leave little to interpretation.

Remove your emotions from the process. Think of it as a business deal – your business. Learn the rules of the game and make the rules work for you. The 'red-tape' and follow-up letters asking for additional information are all part of the game.

Understand how the forms are written. The disability process is written for people with a sudden illness or disability – not for people with progressive illnesses where there is no treatment or cure.

Understand the process. Remember that the Social Security Administration is a government agency. Applications are denied the first time if insufficient information is there to make your case. 

Other comments on SS-D 

Document everything. The more information and details you can provide up front, the smoother the process will go.

Provide a history of the progression. You have been living with this condition for years. Include falls, injuries, hospitalizations, problems with performing certain tasks, etc.

Educate the reviewer. Do not expect the reviewer to understand Kennedy's Disease or your specific situation. The reviewer can be an excellent advocate if he/she understands Kennedy's Disease and your specific disabilities in regards to work. Give the person all the information they need to understate your condition. As much as possible, relate symptoms and progression to other similar conditions that are more recognizable, i.e., ALS, Muscular Dystrophy, and Huntington’s Disease.

Preparation is the key. The more prepared and organized you are, the better the chance for approval. (For example, I was approved in six weeks)

Make it easy for others. Below are several comments on how to help ease the reviewer (and others) through your disability application process. The easier it is for them, the easier it will be for you, and the better chance for approval.

Employer: Discuss your intentions with Human Resources and your manager or supervisor. Ask for their support. You do not want them to be surprised when a Social Security representative contact them asking for information.

Neurologist: Advise your doctor(s) and his/her staff that you are applying for Social Security-Disability benefits. Ask the doctor(s) for his/her support. Review (preferably in written form) your current symptoms and any health-related issues that affect your ability to perform your current duties.

Initial submission: Provide the reviewer with as much information as possible. The more information the reviewer has to work with initially, the less information he/she has to write off for – meaning a delay in the process. The more information requested by the reviewer, the greater the chance the doctor's office will not be able to find it and/or it will be delayed.

Tell your story: Control the information flow. The most important information should be in the front. Sections should be tabbed and key statements/information highlighted so the reviewer can easily find the critical information he/she needs to make a decision. 

Use the 'Supplemental Section' to educate the reviewer: The reviewer probably has never heard of SBMA. Tell them about Kennedy's Disease, its symptoms, its treatment, etc. There are excellent articles on the KDA website and on the internet that explain the disease to a layman.

Provide the information in a 'report' format: Tabbed, with sections, page numbers, a table of contents, etc. - so the reviewer can easily locate the information he/she is looking for. I submitted a three-ring binder. Keep a duplicate three-ring binder of all the submitted information. This will keep all of your information in one place and easy to find.

Review before submitting: Dot the i’s and cross the t’s: Be sure to sign and date all the forms. Have someone else review the submission to make certain they understand it and can find the information needed. 

A Few More Suggestions 

• If called, refer to the information needed by section and page number so the reviewer can easily find what he/she is looking for. 

• Take your binder with you to any reviews or hearing. 

• Be patient and responsive to follow-up inquiries by the reviewer. 

• Follow-up with your doctor, H.R. and supervisor to insure they provided the requested information. I asked for copies of their submissions and added them to my binder. 

How long does the process take? Plan on 60 to 90 days. It generally takes longer to process claims for disability benefits than other types of Social Security claims. You can help shorten the process by bringing certain documents with you when you apply and helping the SSA to get any other medical evidence they need to show you are disabled. The points mentioned below will help shorten the process. 

Be prepared to provide:

• Your Social Security number and proof of age 

• Names, addresses and phone numbers of doctors, hospitals, clinics and institutions that treated you and dates of treatment 

• Names of all medications you are taking 

• Medical records including test results from your doctors, therapists, hospitals, clinics and caseworkers 

• Your work history. A summary of where you worked and the kind of work you did 

• A copy of your W-2 Form (Wage and Tax Statement), or, if you are self-employed, your federal tax return for the past year 

• Family information including names and dates of marriages and your children’s births. 

Do not become frustrated. It is not uncommon to be denied the first time. If that happens, schedule a meeting with your local Social Security Representative to review your application and ask for their opinion why the application was denied. Try to remove your emotions from this discussion. It is easy to become frustrated and start blaming the system or others, but it will not speed up the process. Work with your representative to resolve any known issues with the application or concerns with your claim. The representative can be a great advocate. Then, file an appeal.

To learn more about the application process, contact your local Social Security Administration office, by going online to (http://www.ssa.gov/disability/) or, by calling 1-800-772-1213.

The PDF guide I wrote can be found here: https://www.kennedysdisease.org/images/stories/PDFs/Social_Security-Disability.pdf

I hope this brief post helps to explain the process and some key 'learnings' based upon my experience. Should you have additional questions or comments, please don’t hesitate to contact me.

Huntington’s breakthrough

I have mentioned in earlier articles that Huntington’s Disease share a common genetic defect. It was first reported several years ago a PubMed article links acommonality between HD, KD and SCA-1.

“…Three neurodegenerative diseases, Huntington's disease (HD), Kennedy's disease (hereditary spinobulbar muscular atrophy, SBMA), and type 1 spinocerebellar ataxia (SCA-1) have been found to share a common genetic defect: an unstable region of repeated CAG trinucleotides…”

This morning I read a BBC News report about a potential breakthrough in the treatment and possible cure of Huntington’s Disease. This appears to be another positive step forward in search of an eventual treatment or cure for Kennedy’s Disease.

Huntington’s breakthrough may stop disease

James Gallagher, Health and science correspondent, reports: “…The unstoppable death of brain cells in Huntington's leaves patients in permanent decline, affecting their movement, behaviour, memory and ability to think clearly.

• Huntington's generally affects people in their prime - in their 30s and 40s
• Patients die around 10 to 20 years after symptoms start
• About 8,500 people in the UK have Huntington's and a further 25,000 will develop it when they are older Huntington's is caused by an error in a section of DNA called the huntingtin gene.
• Normally this contains the instructions for making a protein, called huntingtin, which is vital for brain development. But a genetic error corrupts the protein and turns it into a killer of brain cells.

The treatment is designed to silence the gene…”

“…On the trial, 46 patients had the drug injected into the fluid that bathes the brain and spinal cord. The procedure was carried out at the Leonard Wolfson Experimental Neurology Centre at the National Hospital for Neurology and Neurosurgery in London. Doctors did not know what would happen. One fear was the injections could have caused fatal meningitis. But the first in-human trial showed the drug was safe, well tolerated by patients and crucially reduced the levels of huntingtin in the brain…”

This is another article snipped from the NIH.gov blog. Since Huntington’s and Kennedy’s Disease  both have extra repetitions of the CAG DNA, this is another advancement in treating and possibly curing these type diseases. As I mentioned in my previous post, the process is still experimental, but it is moving in the right direction. If you haven't read the previous update on gene editing, you can find it here.

To read the entire article, click on the title below.

Huntington’sDisease: Gene Editing Shows Promise in Mouse Studies

Posted on June 27, 2017 by Dr. Francis Collins

“…But years of basic science advances, combined with the promise of innovative gene editing systems such as CRISPR/Cas9, are providing renewed hope that we will someday be able to treat or even cure Huntington’s disease, along with many other inherited disorders.

My own lab was part of a collaboration of seven groups that identified the Huntington’s disease gene back in 1993. Huntington’s disease occurs when a person inherits from one parent a mutant copy of the huntingtin (HTT) gene that contains extra repetitions, or a “stutter,” of three letters (CAG) in DNA’s four-letter code. This stutter leads to production of a misfolded protein that is toxic to the brain’s neurons, triggering a degenerative process that, over time, leads to mood swings, slurred speech, uncontrolled movements, and, eventually, death. In a new study involving a mouse model of Huntington’s disease, researchers were able to stop the production of the abnormal protein by using CRISPR tools to cut the stutter out of the mutant gene.

The progress, reported in the Journal of Clinical Investigation [1], comes from the NIH-supported team of Su Yang, Renbao Chang, Xiao-Jiang Li, and colleagues at Emory University School of Medicine, Atlanta. The group’s previous work showed that halting the production of mutated (or even healthy!) HTT protein in mature neurons doesn’t hurt the cells or cause obvious neurological problems in mice [2]. So, the researchers now wanted to see if halting HTT production in millions of neurons in the striatum, which is a part of the inner brain that controls motor skills, could reverse early signs of disease that typically appear in affected mice before the age of 9 months.

To get their answers, the researchers injected millions of inactivated viral particles directly into the striatum of a few 9-month-old mice, engineered to produce the mutant form of HTT protein. Each particle, like a Trojan horse, delivered to the neurons one of the two pieces of the CRISPR/Cas9 editing system: either a short guide RNA sequence to mark for removal the HTT gene’s CAG repeats or a scissor-like Cas9 enzyme to snip out the repeats. In this strategy, both the health and abnormal copies of the HTT gene were “knocked out,” resulting in the production of no HTT protein.

Remarkably, three weeks later, the researchers found that the CRISPR/Cas9 gene editing had reversed the disease process in their mouse model. Neurons in the striatum had stopped making the HTT protein. What’s more, the toxic, abnormal HTT protein that had already clumped together in and around the neurons—and which likely would have would have killed them—had begun to clear to varying degrees in the mice. The same went for other protein abnormalities associated with the progression of Huntington’s disease.

There was even better news to come. The Emory team repeated the CRISPR/Cas9 injections into the striatum of a dozen 9-month-old mice and got a similar protein-clearing outcome. Then, over the next three months, the researchers found that the animals’ balance, muscle coordination, and mobility had improved compared to mice given sham shots of CRISPR/Cas9. Interestingly, the degree of improvement in their motor skills corresponded with the amount of toxic protein that had been cleared from the striatum…”

“…This utilization of CRISPR/Cas9 to pursue a cure for Huntington’s disease is one more example of how this powerful new technology might be applied to the thousands of diseases due to a specific mutation in DNA; efforts are already underway for other conditions like sickle cell disease and muscular dystrophy. Given the promise, the NIH Common Fund is actively exploring ways in which this approach could be accelerated.”

SBMA and HD; New Genetic Study of HD

An article published last month in HDBuzz discusses Huntington's Disease (HD). Since HD and Kennedy's Disease (SBMA) have defects of the CAG genes, there are similarities between the two conditions.

Important drug targets yielded by new genetic study of HD

A genetic study confirms that minute differences in DNA repair genes can influence the age of HD symptom onset.
By Leora Fox on May 02, 2016Edited by Dr Jeff Carroll

It’s a great mystery why different people with the same HD mutation sometimes develop symptoms at vastly different ages. Last year a huge genetic analysis gave us some interesting clues, and now, researchers are focusing in on the most promising results. A recent study shows that tiny changes within genes that repair damaged DNA can have a big effect on age of onset in HD and related diseases.

Pursuing the reasons for different ages of symptom onset

Huntington’s disease is an inherited illness, so a person whose parent or grandparent has the disorder is at risk of developing symptoms one day. Even those who learn they are positive for the HD gene through genetic testing face a great and daunting unknown: when will symptoms begin to develop? ...

... In fact, HD is not the only polyglutamine disorder – several other hereditary illnesses are caused by CAG repeats in different parts of the genome. Two examples are spinocerebellar ataxia (SCA), which involves difficulties with balance and coordination, and spinal bulbar muscular atrophy (SBMA), which usually affects men and causes muscle weakness and hormone imbalances. One similarity between CAG repeat diseases is that longer repeats cause earlier ages of symptom onset. And it turns out that some of the same genetic modifiers that contribute to the timing of HD symptoms play a similar role in other poly-Q diseases. ...

... We don’t yet understand the reasons why such tiny changes in DNA repair genes led to significant discrepancies in age of onset in poly-Q disorders. Nevertheless, it is exciting to unearth direct genetic evidence that a shift in symptom onset is possible. ...

To read the entire article including the section on SBMA, follow this link: https://en.hdbuzz.net/217

Gene Therapy for Neurodegenerative Diseases

SMA News Today published an interesting article. Perhaps another opportunity for us living with Kennedy's Disease.

INT41 Gene Therapy for Neurodegenerative Diseases Granted Priority Patent Status

The patent application for gene therapy candidate1 INT41, developed by Vybion for the treatment of Huntington’s disease, spinal muscular atrophy (SMA), and other neurodegenerative diseases, was granted Track One status from the U.S. Patent and Trademark Office (USPTO).

The patent application covers the treatment’s composition and methods of use. The Track One designation gives the application priority review, allowing it to get a final decision within about a year. Track One has fewer requirements and doesn’t need a pre-examination search for the application.

“Vybion is pleased to receive Track 1 status on INT41 and anticipates rapid review and allowance,” Vybion CEO Lee Henderson said in a press release.

INT41 gene therapy was specifically designed to target neurologic diseases caused by polyQ expansions, resulting in mutant proteins that accumulate in motor neurons and subsequently lead to cellular degeneration. The gene therapy aims to detect and target the “toxic” sequence, promoting its degradation and thereby preventing its accumulation in neuronal cells. ...

... INT41 is considered a potential therapeutic strategy for other neurodegenerative diseases with similar biological features, such as spinal cerebellar ataxia, Alzheimer’s disease, and spinal and bulbar muscular atrophy (SBMA). However, the treatment has so far been more fully developed for Huntington’s, according to Vybion’s drug pipeline, and more studies are required to validate its effectiveness and safety for it and other neurodegenerative conditions. ...

To read the entire article click on the title above.

For those that want to read the actual study, follow this link. Journal of Neurodegnerative Diseases

Human Gene Editing

I have written posts a few times in the past about CRISPR, a technology that allows the editing of human genes. In my current book I'm writing, the idea of gene editing is an important aspect of creating super-healthy children.

The New York Times published the following article today. As with anything revolutionary in nature, their is controversy surrounding it.

Human Gene Editing Receives Science Panel’s Support

"An influential science advisory group formed by the National Academy of Sciences and the National
Academy of Medicine on Tuesday lent its support to a once-unthinkable proposition: the modification of human embryos to create genetic traits that can be passed down to future generations.

This type of human gene editing has long been seen as an ethical minefield. Researchers fear that the
techniques used to prevent genetic diseases might also be used to enhance intelligence, for example, or to create people physically suited to particular tasks, like serving as soldiers.

The advisory group endorsed only alterations designed to prevent babies from acquiring genes known to cause “serious diseases and disability,” and only when there is no “reasonable alternative.” The report provides an explicit rationale for genetic research that the federal government has avoided supporting until now, although the work is being pursued in countries like Sweden and China.

So-called germ line engineering might allow people to have biological children without fear that they have passed on the genes for diseases like Huntington’s, Tay-Sachs and beta thalassemia, and without discarding embryos carrying the disease-causing mutations, as is often done now. Though such cases are likely to be rare, the report says they should be taken seriously. ..."

Follow the link above to read the rest of the article.

Kennedy's Disease Research; Future possibilities in

Last Saturday, Ed Meyertholen, the KDA's resident biology professor, was the KDA's Forum guest. As always, Ed provides information in a manner that is understandable to almost any audience.

Below are some of Ed Meyertholen’s comments and answers to specific questions concerning CRISPR and iRNA research. To read the entire forum discussion, follow this link: http://www.kennedysdisease.org/index.php/provide-support/chat-room-transcripts/2016-chat-room-transcripts/627-2016-february-06 .

“I am not a CRISPR expert, but the technique has been quickly (in the science view of quickly - several years) improving and it is expected that it will continue to do so. I do not think we will see this in humans for a while (years). 

In KD, I can imagine there may be issues on specificity - what cells to send CRISPR to, nerve cells or muscle (or both) and then one has to develop the procedures to specify the cells. The CRISPR work is very new and I do not know if anyone is working on it in Kennedy’s Disease. I suspect that someone will be soon. Nonetheless, I think that it has great possibilities - and I am usually not too optimistic. 

What happens is that they use a virus that normally attacks a specific cell type (like muscle), remove the DNA from the virus and replace it with the DNA needed to get CRISRP to work. The virus with the CRISPR DNA in injected into blood, goes to the muscle cells and instead of injecting viral (bad) DNA, injects the CRISPR DNA. The CRISPR DNA then lets the muscle cells make the CRISPR proteins which then should (and in the mouse, did) alter the DNA in those cells only. DNA in other than muscle cells is not affected. 

Kennedy’s Disease may give rise to other issues - the androgen receptor (the mutated protein) is made in many cells and may have effects (sexual issues, gynomatica (sp)), so we might want to alter the gene in other cells as well. It has great possibilities but it is not ready for prime time yet. This is the CRISPR paper:  http://www.ncbi.nlm.nih.gov/pubmed/26721684.

There was another paper from NIH (Kurt's lab) where they used iRNA to block the synthesis of the mutant androgen receptor and found that the mice got better. This is similar to work from LaSpada and from Lieberman that had been published a few years ago. These were done in conjunction with drug companies and I would not be surprised if there would be a clinical trial (I think that there is one starting using the same technique in Huntington's Disease) now. The other techniques with iRNA or ISO's are much closer to clinical use. If I remember correctly getting to nerve cells requires getting past the blood-brain barrier issue(s). Kurt's paper is here - http://www.ncbi.nlm.nih.gov/pubmed/26755334 .”

Photo:  http://www.science.ca/images/altman_rnase.jpg

The Annual Kennedy's Disease Conference was held in Chicago this year. The post-conference newsletter is now available for reading (PDF) online. There are several excellent articles on current research as well as plenty of conference news. I have copied a couple of the articles that might be of interest.

____________________________

Research News at the 2015 KDA Conference
Ed Meyertholen, Ph.D.
KDA Board Member, and Scientific Review Board Member
Assistant Dean, Georgetown College, Georgetown University, Washington, DC

The annual conference of the Kennedy’s Disease Association was held this past October in Chicago. We are lucky in that we have a group of researchers that not only are dedicated to finding a treatment for KD but also able to find time to present their most recent research at the meeting. In addition, our meetings also allow for the interaction between the researchers and the conference attendees. This is by far the most rewarding part of the conference for me personally.

As is typical, researchers who came to the meeting were from most of the labs in the USA and Canada that make major contributions to KD research as well as some from across the pond. The research described at the meeting is generally unpublished work and as a result, is not usually ready for broad distribution. For me, however, one of the more interesting and encouraging developments this year actually was not a part of our conference and did not even deal with KD but its close cousin, Huntington’s Disease (HD). A new clinical trial using something called anti-sense oligonucleotides (ASO) had started this summer. Without going into excruciating details, ASO’s prevent the production of the protein that causes HD and as a result, the symptoms of HD in mice were reduced with the injection of this ASO. The success of these experiments in mice led to the formation of the clinical trial to use ASO’s in humans. Experiments using ASO’s against the androgen receptor (the protein affected in KD) in mice have also shown to be effective in relieving symptoms of KD. Thus, if this treatment works in HD patients, it should work in KD as well.

The KDA Conference is also the site of the notification and presentation of the research grants funded by the KDA. This year, thanks to your donations and fund raisers two grants were awarded at the conference, one to Dr. Miltiadis Paliouras (principle investigator) and Dr. Lenore Beitel (co-applicant) who are Assistant Professors at McGill University; and the other to Dr Constanza Cortes, a post-doctoral researcher in Al La Spada’s lab at UC-San Diego. The competition for the grants was extremely fierce this year as a record number of proposals were submitted – all of them of excellent quality.

____________________________

Exercise Research 

Joseph A Shrader, PT, C.Ped 

Senior Clinical and Research Physical Therapist, Clinical Research Center, NIH

Recent evidence suggests that functional exercises aimed at improving functional tasks such as

sitting up, rolling over, sit-to-stand, and stepping up an 8-inch step were well tolerated by persons with spinal and bulbar muscular atrophy when supervised by rehabilitation and/or nursing professionals. Overall, strength, balance, function, and quality of life did not differ between those who received the exercise versus stretching (control group), however, those with relatively low baseline function improved their functional profile and those with relatively high baseline function improved their general activity level, compared with the control group. More research is needed to help optimize exercise intensity, mode, frequency and duration for individuals with KD. General recommendations for people with KD include attempting to incorporate daily physical activity into your lifestyle, along with good nutrition and sleep habits. If you experience falls, fear of falling, leg weakness, requirement of assistance or assistive devices for standing and walking, it is recommended that you first be examined by your primary doctor, neurologist, or physiatrist to discuss contraindications and exercise goals. It is also recommended that exercises be initially prescribed and monitored for appropriate post-exercise recovery by a physical therapist, until a safe and sustainable self-directed program can be assured.

NIH does not endorse or recommend any commercial products, processes, or services. The views and opinions of NIH authors do not necessarily state or reflect those of the U.S. Government, and they may not be used for advertising or product endorsement purposes.

Clinical Trial News on Huntington's Disease

Why an update on Huntington's Disease? Good question.

Huntington's Disease is in a similar category to Kennedy's Disease (SBMA). The hope is that a treatment or cure for a similar condition might lead towards something to help those of us living with Kennedy's Disease.

First patients dosed with 'gene silencing' drug for Huntington's disease

October 19, 2015

The first few patients have received doses of an experimental RNA-targeting drug for Huntington's disease, it was announced today.

The trial aims to test the safety of an experimental drug known as ISIS-HTTRx, discovered and developed by Isis Pharmaceuticals. Administered by injection into spinal fluid to improve its delivery to the brain, the drug is the first tested in patients that targets the known cause of the disease: a toxic protein called mutant huntingtin which slowly damages and kills neurons, leading to the progressive and ultimately fatal decline in mental and physical abilities that is the devastating hallmark of Huntington's disease.

The huntingtin gene and its lethal protein product have been the focus of intense research across the world since their discovery in 1993. 'Gene silencing' drugs, also known as 'antisense' drugs, are designed to reduce production of a chosen protein by attaching to the mRNA 'message molecule' that's made whenever a gene is activated. ISIS-HTTRx targets the huntingtin message molecule, telling the cell to dispose of it, thereby reducing production of the mutant huntingtin protein.

There are no treatments to prevent, slow or cure Huntington's. RNA-targeting antisense drugs, like ISIS-HTTRx, that lower huntingtin production are widely considered the most promising therapeutic strategy currently under investigation. Isis's Huntington's disease therapeutics underwent over a decade of refinement and preclinical testing before human trials could begin. The first Phase 1/2a trial is focused principally on safety, using slowly increasing doses of ISIS-HTTRx with careful monitoring of patient wellbeing, scans and laboratory parameters. In addition, the researchers will be looking for chemical signs that the drug is having the desired effect - by measuring the level of mutant huntingtin protein in the cerebrospinal fluid using a newly developed assay. ...

To read the rest of the article, follow this link:  http://medicalxpress.com/news/2015-10-patients-dosed-gene-silencing-drug.html

Clinical Trial for HD

This could be important to those of us living with Kennedy's Disease. Huntington's Disease (HD) is similar to Spinal Bulbar Muscular Atrophy in that it is also a CAG Triplet Repeat Disorder that previously did not have any treatment. If successful, the drug will target the cause of HD.

___________________

Press Release

Isis Pharmaceuticals Initiates Clinical Study of ISIS-HTT Rx in Patients With Huntington's Disease

First therapy designed to directly target the cause of disease Isis Earns $22 Million Milestone Payment from Roche   CARLSBAD, Calif., July 21, 2015 /PRNewswire/ -- Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) today announced that it has initiated a Phase 1/2a clinical study of ISIS-HTTRx in patients with Huntington's disease (HD). ISIS-HTTRx is the first therapy to enter clinical development that is designed to directly target the cause of the disease by reducing the production of the protein responsible for HD. HD is a rare genetic neurological disease in which patients experience deterioration of both mental abilities and physical control. Presently, there are no disease-modifying treatments for HD, with current therapies focused only on treating disease symptoms.   ISIS-HTTRx has been granted orphan drug designation by the European Medicines Agency for the treatment of patients with HD.  Orphan drug designation is granted to products designed to diagnose, prevent or treat life-threatening or very serious conditions that affect not more than five in 10,000 persons in the European Union.   "Although the toxic protein produced from the huntingtin (HTT) gene in HD patients has been a target of interest for many years, no therapies have advanced to clinical trials to treat the underlying cause of the disease. Our antisense technology has enabled us to discover and develop ISIS-HTTRx, the first therapeutic approach designed to treat the genetic cause of HD. Together with Roche, we are committed to investigating this approach to treat patients with HD, a devastating disease that typically affects generations of families," said C. Frank Bennett, Ph.D., senior vice president of research at Isis Pharmaceuticals. "Initiating the clinical study of ISIS-HTTRx in patients with HD is the first step in developing a treatment that could significantly impact a patient's disease. It is also an important milestone in our collaboration with Roche. As we advance this program, we will continue to benefit from Roche's scientific expertise in developing therapeutics for neurodegenerative conditions," said B. Lynne Parshall, chief operating officer of Isis Pharmaceuticals. The randomized, placebo-controlled, dose escalation Phase 1/2a clinical study will evaluate the safety and activity of ISIS-HTTRx  in patients with early stage HD.  In this study, ISIS-HTTRx  will be administered intrathecally as an injection directly into the cerebral spinal fluid. Intrathecal administration of antisense drugs has been shown to be well tolerated in multiple clinical studies in patients. "The initial development of this antisense drug for Huntington's disease came out of a longstanding productive partnership between Isis and CHDI, and its advancement now to clinical trial is testament to Isis' perseverance and scientific expertise," said Robi Blumenstein, president of CHDI Management, which oversees the activities of CHDI Foundation, a nonprofit research organization exclusively dedicated to the development of therapies that will slow the progression of HD. "It's exciting that therapeutic candidates grounded in the biology of Huntington's disease are finally making their way to clinical trial." ABOUT ISIS and ROCHE Roche and Isis are collaborating to develop antisense drugs to treat HD. The alliance combines Isis' antisense expertise with Roche's scientific knowledge in developing neurodegenerative therapeutics. With the initiation of the Phase 1/2a study for ISIS-HTTRx, Isis earned a $22 million milestone payment from Roche. To date, Isis has earned $52 million in upfront and milestone payments from its relationship with Roche and is eligible to earn additional milestone payments as the drug progresses in development, as well as royalties on sales of ISIS-HTTRx if it is commercialized. Roche has the option to license ISIS-HTTRx from Isis through the completion of the Phase 1/2a study. Prior to option exercise, Isis is responsible for the discovery and development of ISIS-HTTRx. If Roche exercises its option, it will assume responsibility for global development, regulatory and commercialization activities for the drug. CHDI Foundation, Inc. provided financial and scientific support to Isis' HD drug discovery program through a development collaboration with Isis. Over time, CHDI will be reimbursed for its support of Isis' program out of milestone payments received by Isis. ABOUT ISIS-HTTRx and Huntington's Disease ISIS-HTTRx is a Gen. 2.0+ antisense drug in development for the treatment of Huntington's disease. ISIS-HTTRx  is designed to reduce the production of all forms of the huntingtin protein, which is the protein responsible for HD. As such, ISIS-HTTRx offers a unique approach to treat all patients with HD. HD is a rare genetic, progressive neurological disease resulting in deterioration in mental abilities and physical control. HD is referred to as a triplet repeat disorder, and is one of a large family of genetic diseases in which certain gene sequences are mistakenly repeated. In HD, the gene that encodes for the HTT protein contains a trinucleotide sequence that is repeated in the gene more than 36 times. The resulting HTT protein is toxic and gradually damages neurons in the brain. Symptoms of HD usually appear between the ages of 30 to 50 years, and continually worsen over a 10 to 25 year period. Ultimately, the weakened individual succumbs to pneumonia, heart failure or other complications. Presently, there is no effective disease modifying treatment, and current approaches only focus on managing the severity of some disease symptoms.