Wednesday, March 20, 2019

SBMA Patients are More Likely to be Affected by Metabolic Disorders, Heart and Liver Disease

The following was reported in SMA News Today. The information is not new and from my perspective reflects mainly on the sedentary lifestyle after the progression has reached a point where the person can no longer perform aerobic physical exercise.

I believe it also reflects the need to continue to exercise (safely), change your diet, and be mindful of the possibility of these conditions in discussions with your doctor.

Heredity also plays an important factor in many of these conditions. 

SBMA Patients are More Likely to be Affected by Metabolic Disorders, Heart and Liver Disease

Patients with spinal-bulbar muscular atrophy (SBMA) are more likely to be affected by metabolic disorders, including insulin resistance and fatty liver disease, which can lead to heart disease and serious liver damage, a study says.

The study, “Prevalence of metabolic syndrome and non-alcoholic fatty liver disease in a cohort of Italian patients with spinal-bulbar muscular atrophy,” was published in Acta Myologica.

SBMA, also known as Kennedy’s disease, is a type of spinal muscular atrophy (SMA) that starts in adulthood and is characterized by widespread muscle weakness and wasting in the arms, legs, head, and neck (bulbar involvement).

The disorder is caused by mutations in the androgen receptor (AR) gene — located on the X chromosome — that lead to an abnormal expansion of a CAG nucleotide (the building blocks of DNA) repeat in the AR gene sequence and to the production of a much larger dysfunctional protein.

Besides neurologic symptoms, SBMA patients also tend to be affected by medical conditions associated with metabolic syndrome (a series of conditions that increase patients’ risk of developing heart disease, stroke or type 2 diabetes), such as insulin resistance, obesity, and glucose intolerance.

In the study, researchers at the University of Padua, in Italy, assessed the incidence of metabolic syndrome, insulin resistance, and non-alcoholic fatty liver disease (NAFLD) in a group of SBMA patients.

The study involved a total of 47 Italian patients with a confirmed diagnosis of SBMA who underwent a battery of biochemical tests to assess metabolic functions. A subset of 24 patients were examined by abdominal sonography (an imaging technique that allows physicians to visualize structures in the patients’ abdominal cavity).Results showed that 49% of the patients had abnormally high levels of fasting glucose (commonly used to diagnose diabetes), and 66% showed signs of insulin resistance.

In addition, 51% of the patients had high levels of total cholesterol, 38% had high LDL-cholesterol (“bad” cholesterol), and 38% had high triglycerides. Conversely, 77% had low levels of HDL-cholesterol(“good” cholesterol). More than half of the patients (55%) had three or more medical conditions associated with metabolic syndrome.

Researchers also found a positive relationship between insulin resistance and the length of CAG repeats in the AR gene sequence.

Biochemical tests showed high levels of two liver enzymes that, when elevated, may indicate liver inflammation or damage: aspartate transaminase (AST) levels were abnormally high in 62% of patients, and alanine transaminase (ALT) levels were high in 38% of patients.

Abdominal sonography revealed that 92% of the patients had liver steatosis (fatty liver disease) at different levels of severity, and one patient had liver cirrhosis (scarring of the liver).

“These alterations can be explained mainly by the reduction of testosterone activity because of (CAG repeats’) expansion in AR gene and must be considered as a main characteristic of Kennedy’s disease,” the researchers wrote.

“Metabolic alterations in SBMA are a suggestive model of androgen deprivation in male and require a multidisciplinary approach to disease. However, considering the conflicting data on the role of androgen stimulation in the metabolic involvement, further studies are needed to understand the pathogenesis of NAFLD and (insulin resistance) in SBMA patients and the possible detrimental consequences of anti-androgen approaches to disease,” they concluded.

Sunday, March 17, 2019

Report on the ENMC Conference

I wish to thank the Kennedy's Disease Association (KDA) for sharing this report from the recent European Neuro Muscular Centre Conference (ENMC). 

I feel this is a major step forward in finding a treatment for SBMA.  

Towards a European Unifying Lab for Kennedy's Disease

Twenty-four scientists working in academia, hospitals and industry from 8 different countries (Denmark, France, Germany, Israel, Italy, Spain, United Kingdom, USA) along with three patients’ representatives, (one who was also a representative of the USA patient group, The Kennedy’s Disease Association), met in the Netherlands on the weekend of the 15th- 17th of February 2019. They discussed the recent developments in research and shared the most recent clinical observations in spinal and bulbar muscular atrophy (SBMA). The workshop was conducted under the leadership of Maria Pennuto, Gianni Sorarù, Linda Greensmith and Pierre-Francois Pradat.

Background and Aims of the Workshop

SBMA, also known as Kennedy’s disease, is a rare, adult onset, neuromuscular disease caused by a mutation in the gene encoding for the protein which binds the male hormone androgen. This protein is called the Androgen Receptor (AR). The mutation is carried on the X chromosome and because the effects of the mutation are dependent on the presence of the male hormone androgen, the disease only affects males. However, females can be carriers of the mutation and if they do show symptoms, these tend to be mild.

The Androgen Receptor has an essential role in mediating the effects of the male hormone, androgen, and, when mutated, leads to muscle fatigue, weakness and atrophy of the arm and leg muscles, along with problems in speech, chewing and swallowing. Twitching or cramping of muscles can also occur.

Significant improvements have been made over the last few years in both our understanding of pathological mechanisms underlying the disease as well as in a greater recognition of the varied clinical manifestations of SBMA and in the development of clinical evaluation tools which together are essential to undertake effective therapeutic trials.

The aim of this workshop was to bring together leading clinical and basic scientists working in the field of SBMA to discuss the current understanding of basic disease mechanisms and to share and update the most recent developments in clinical evaluation of patients, with the objective of increasing the prospects of developing and testing new treatments that could effectively slow down disease progression in SBMA patients. ...

... Next Steps

In order to increase scientific and clinical collaborations between groups working in different countries, it was agreed that the First International Conference on SBMA will be organized, to be held in the spring 2020. The researchers and clinicians have underlined the need to collaborate with patients’ associations in the organization of the meeting with the aim of reinforcing the communication of scientific and clinical progress to SBMA patients and families, and providing the community with the possibility to directly collaborate in the research process.

Click here to read the entire report

Saturday, March 16, 2019

Leuprorelin Acetate May Reduce Swallowing Dysfunction

The following article was published in SMA News.  The study was 48 weeks long and included 283 patients with Kennedy' Disease.

Leuprorelin Acetate May Reduce Swallowing Dysfunction in SBMA Patients, Study Finds

By Joanna Carvalho

Leuprorelin acetate may be a promising therapy to minimize swallowing dysfunction in patients with spinal and bulbar muscular atrophy (SBMA), a study finds.

The study, “Efficacy and safety of leuprorelin acetate for subjects with spinal and bulbar muscular atrophy: pooled analyses of two randomized-controlled trials,” was published in the Journal of Neurology.

SBMA, also known as Kennedy’s disease, is a type of spinal muscular atrophy (SMA) that starts in adulthood and is characterized by widespread muscle weakness and wasting in the arms, legs, head, and neck (bulbar involvement). For this reason, besides having impaired mobility, SBMA patients may have difficulties swallowing and speaking.

The disorder is caused by mutations in the androgen receptor (AR) gene — located on the X chromosome — which provides instructions for the androgen receptor protein. Although this protein is present everywhere in the body, it is enriched in motor neurons, the nerve cells responsible for controlling voluntary movements that are gradually destroyed in patients with SMA.

Because the the AR gene affects the body’s response to androgens — the male hormones involved in sexual development, such as testosterone — patients may have other symptoms, including infertility and erectile dysfunction (male impotence).

After the discovery of the AR gene, studies in animal models of disease revealed SBMA is triggered by the interaction of androgens with the defective androgen receptors. For this reason, treatment for SBMA has centered on the development of therapies involving androgen deprivation.

“Successful treatment of SBMA in mouse models with castration or administration of leuprorelin acetate, a luteinizing hormone-releasing hormone (LH-RH) agonist that reduces testosterone release from testes, supported the idea that testosterone blockade therapy could be beneficial and enabled subsequent human clinical trials,” the study stated.

In the study, Japanese researchers performed a pooled analysis of two identical randomized, placebo-controlled, double-blind clinical trials — JASMITT-06DB and JASMITT-11DB — to evaluate in more detail the efficacy and safety of leuprorelin acetate in patients with SBMA.

In both trials, patients were randomly assigned to receive either leuprorelin acetate or a placebo (control), once every 12 weeks, for 48 weeks. The primary goal was to assess changes in the amount of barium residues (a contrast agent used to visualize structures in the body) in the pharynx (throat) when patients attempted to swallow. Secondary measures included blood tests to measure testosterone levels, scrotal skin biopsies, and quality of life assessments.

In total, 283 SBMA patients were enrolled, including 142 who were treated with leuprorelin acetate and 141 with placebo.

Patients treated with leuprorelin acetate and those treated with placebo had an average decrease of 4.12% in the amount of barium residues present in the pharynx after initial swallowing. Although differences between the two groups after initial swallowing suggested that leuprorelin acetate might be effective at each assessment point, the changes from the initial visit to the last were not statistically significant between both groups, and the primary objective was not reached.

In general, leuprorelin acetate treatment was well-tolerated. The incidence of side effects (81.7% taking leuprorelin and 80.1% in the placebo group) and drug-related side effects (62.7% taking leuprorelin and 53.9% in the placebo group) were similar between the two groups.

However, some of the side effects, including abnormal liver function, weight gain, skin reactions at the injection site, decreased libido, erectile dysfunction, and excessive sweating, were more severe in patients treated with leuprorelin acetate than in those treated with placebo.

“In conclusion, leuprorelin acetate may be safe and beneficial for improvement of swallowing dysfunction in the patients with SBMA, without increasing the number of serious side effects,” the researachers said. “Further investigations are needed to clarify the efficacy of this therapy for SBMA.”

Monday, March 4, 2019

New Gene Therapy Approach Able to Repair Mutations

Below is a small portion of the article in SMA News. Since the focus is on repairing triplet disorders, Kennedy's Disease (SBMA) could also benefit.

New Gene Therapy Approach Able to Repair Mutations Causing SMA, Other Inherited Diseases, Mouse Study Suggests

A new gene therapy approach using RNA molecules called transfer RNAs (tRNAs) was able to repair a subset of mutations causing spinal muscular atrophy (SMA) and other inherited diseases in living muscle tissue of mice, a study shows.

These genetic alterations, called nonsense mutations, alter the DNA sequence and introduce so-called stop codons — triplets of nucleotides, which are the building blocks for DNA — that prematurely stop gene expression and impair protein production. Besides SMA, these mutations also underlie diseases such as Duchenne muscular dystrophy, cystic fibrosis, and polycystic kidney disease.

The study, “Engineered transfer RNAs for suppression of premature termination codons,” was published in the journal Nature Communications.

Several lines of research have attempted to find compounds that are able to repair nonsense mutations. However, previous research has shown that certain small molecules can generate a different type of mutation that is able to disrupt protein function, but they can be toxic to the ears and kidneys. In addition, using the CRISPR/Cas9 gene editing technique — a potential treatment for diseases caused by nonsense mutations — has presented other challenges, such as off-target effects.

Aiming to find a suitable approach with the ability to repair nonsense mutations precisely, a team from the University of Iowa Carver College of Medicine, The Wistar Institute, the Cystic Fibrosis Foundation Therapeutics Lab and Integrated DNA Technologies investigated the potential of using tRNAs.

All genetic information contained within genes (DNA) is ultimately translated into proteins. However, the process is complex, with several steps: DNA is transformed into messenger RNA (mRNA), then a process called translation begins, which results in the production of proteins.

tRNA is a type of RNA molecule that helps decode a messenger mRNA sequence into a protein. Through specific sequences called anticodons, tRNA molecules match up with the corresponding mRNA and deliver the correct amino acid to build a protein in a cellular structure called ribosome.

Researchers engineered tRNAs to recognize and suppress three different stop codons — triplets of nucleotides that prematurely stop gene expression and impair protein production. (Gene expression is the process by which information in a gene is synthesized to create a working product, such as a protein). ...

To continue reading this article, click on this link

Tuesday, February 26, 2019

Muscle Biomarkers Correlate With Severity in SBMA

Neurofilament Light Chain [NfL]
Image: BestPractice

Wikipedia describes Neurofilaments this way: NF are intermediate filaments found in the cytoplasm of neurons. They are protein polymers measuring approximately 10 nm in diameter and many micrometers in length. Together with microtubules and microfilaments, they form the neuronal cytoskeleton. They are believed to function primarily to provide structural support for axons and to regulate axon diameter, which influences nerve conduction velocity. Neurofilaments are found in vertebrate neurons in especially high concentrations in axons, where they are all aligned in parallel along the long axis of the axon forming a continuously overlapping array. In addition to their structural role in axons, neurofilaments are also cargoes of axonal transport. Most of the neurofilament proteins in axons are synthesized in the nerve cell body, where they rapidly assemble into neurofilament polymers within about 30 minutes. These assembled neurofilament polymers are transported along the axon on microtubule tracks powered by microtubule motor proteins. 

Below is a portion of the abstract from a study published February 20th. You can read the entire study (PDF) at . 

Muscle and not neuronal biomarkers correlate with severity in spinal and bulbar muscular atrophy

Objective: To determine whether blood biomarkers of neuronal damage (neurofilament light chain [NfL]), muscle damage (creatine kinase [CK]), and muscle mass (creatinine) are altered in spinal bulbar muscular atrophy (SBMA aka Kennedy's Disease) and can be used as biomarkers for disease severity.

Methods: In this multicenter longitudinal prospective study, plasma and serum were collected from 2 cohorts of patients with SBMA in London, United Kingdom (n = 50), and Padova, Italy (n = 43), along with disease (amyotrophic lateral sclerosis [ALS]) and healthy controls, and levels of plasma and serum NfL, CK, and creatinine were measured. Disease severity was assessed by the SBMA Functional Rating Scale and the Adult Myopathy Assessment Tool at baseline and 12 and 24 months.

Results: Blood NfL concentrations were increased in ALS samples, but were unchanged in both SBMA cohorts, were stable after 12 and 24 months, and were not correlated with clinical severity. Normal NfL levels were also found in a well-established mouse model of SBMA. Conversely, CK concentrations were significantly raised in SBMA compared with ALS samples, and were not correlated to the clinical measures. Creatinine concentrations were significantly reduced in SBMA, and strongly and significantly correlated with disease severity.

Conclusions: While muscle damage and muscle mass biomarkers are abnormal in SBMA, axonal damage markers are unchanged, highlighting the relevant primary role of skeletal muscle in disease pathogenesis. Creatinine, but not CK, correlated with disease severity, confirming its role as a valuable biomarker in SBMA.

Note: The KDA just posted the research on their website. There was also a note from Pietro Fratta, who spoke about his biomarker research at last year's conference:

This work uses blood samples from 93 Kennedy’s patients, alongside controls and samples from models of disease, to look for traces of neuron and muscle damage in Kennedy’s disease. It finds that muscle damage is prominent, whilst neuron damage is below detection levels. This work highlights the role of muscle damage in Kennedy’s disease, which is extremely important for how therapies are designed. Further, this study supports the use of a specific biomarker, creatinine, for Kennedy’s disease clinical trials.

This study was possible only thanks to the incredibly strong participation to research of patients attending the Kennedy’s Clinic at the National Hospital in London and the University of Padova.

Wednesday, February 13, 2019

Stress and its Effect on Your Body

Stress, whether physical, mental or emotional, takes a toll on us. The issue is often exacerbated when we live with Kennedy's Disease (SBMA). If we are not careful, we can find ourselves putting ourselves down because of the loss of capabilities or the fear of placing burdens on loves ones.

Headspace.Com has an article on "How do you speak to yourself." It emphasizes the importance of being kind to yourself.

"It never ceases to amaze me just how unkind we can be to ourselves. And then we wonder why we are unhappy with no peace of mind. But how can we expect anything else when we talk to ourselves harshly? How can the mind be settled and calm when we are constantly being hard on ourselves?..."

"...If you’re not too sure what healthy mind chatter sounds like, then I think the following can be a useful rule of thumb: Pay attention to any negative inner-chatter. Now, if you said the same thing and spoke the same way to a close friend, how would you expect them to react? Likewise, if they said the same thing to you, or spoke in that tone of voice, how would it make you feel? The answers will provide a fair idea about how much the mind needs softening up."

It is important to recognize what pushes our buttons and why it does. The old saying of "counting to ten" is true for handling stress also. Take a step back - and take several deep breaths - inhaling through the nose and exhaling through the mouth. The practice will help calm the mind as well as the body.


Monday, January 28, 2019

Study identifies potential drug for treatment of SBMA

In March of last year I mentioned this article:

Study identifies potential drug for treatment of debilitating inherited neurological disease

An excerpt of the article can be found below Dr. Taylor's update.

I wrote Dr. Taylor today and asked for an update on the research. Below is his reply.

We have been working with the group in Vancouver at the University of British Columbia who developed the MEPB compound and have identified analogs that have even better potency and drug properties. UBC owns the rights. My understanding is that UBC is discussing a licensing agreement with a drug company to further develop this – meaning they will run independent preclinical trials in a mouse model using the newer compound, and pending those results will initiate human clinical trials. This typically takes ~ 2years.

The following is an excerpt from the original Medical Press article. To read the entire article follow this link: Potential Drug Treatment. The St. Jude's website also has the article:  Study Identifies PDT

As always, I appreciate Dr. Taylor and his team's support for finding a treatment for Kennedy's Disease.

March 15, 2018

Dr. Paul Taylor of St. Jude Children's Research Hospital ...

"... and his colleagues were led to seek drugs to treat SBMA because of findings from a previous study in his laboratory. The study pinpointed a molecular niche in the mutant androgen receptor protein that appeared to be a key to driving SBMA symptoms. However, that niche did not seem to be essential to the normal function of the androgen receptor. The study started with fruit flies genetically engineered to have the human androgen receptor, giving the scientists a living "test tube" to explore the effects of mutating the receptor.

"This identification of a small patch of this protein that appeared to be functionally important for driving the disease, but is not essential for most androgen receptor functions, gave us a potential drug target," Taylor said.

Pharmaceutical companies have been developing drugs to target this small patch, called the "activator function-2" or "AF2" domain. The companies were testing the drugs as possible treatments for prostate cancer, which also involves the androgen receptor. Taylor obtained a collection of the test drugs to evaluate for use with SBMA.

Using the genetically engineered flies, the researchers identified two drugs—whose long chemical names are abbreviated TA and MEPB—that alleviated SBMA symptoms. Then, using mice, the scientists determined that MEPB more effectively reached target tissues in the brain and spinal cord.

For their trials of TA and MEPB as potential SBMA treatments, the researchers developed a new genetically engineered mouse model to more accurately mimic the mutation found in men with SBMA. The transgenic mice showed many of the symptoms of humans with the disease.

Researchers found that MEPB effectively alleviated symptoms of SBMA in the mice. "Treating the mice with MEPB forestalled muscle atrophy and prevented loss of their motor neurons, with recovery of their testicles to normal size," Taylor said. "The treatment also protected their ability to walk and their muscle strength and endurance." ..."

Tuesday, January 22, 2019

Swim Training Improves Muscle Function in Mouse Model of ALS, Study Shows

I know of several men with Kennedy's Disease (SBMA) who expressed how good they felt and how much better/safer their exercise routine is in the pool. I never tried it. Below is an article on the benefits of swim training in mouse models with ALS. Clink on the header below to read the entire article or go to the bottom of this page and follow the link to the actual published report.

Swim Training Improves Muscle Function in Mouse Model of ALS

... Findings revealed that ALS mice had reduced muscle strength (70% less between 11 and 15 weeks), and showed significant alterations in energy metabolism (30% less citrate synthase activity, and higher activities of cytochrome c oxidase and malate dehydrogenase), and high levels of oxidative stress markers compared with controls.

However, swim training reduced the loss of muscle strength associated with ALS (5% less between 11 and 15 weeks), and increased citrate synthase activity by 26% compared with ALS mice that did not undergo swim training.

According to previous studies, swim training prolongs the lifespan of ALS mice by 10% to 13%. However, “from a clinical point of view, not only prolongation of lifespan, but also sustained functionality and inhibition of muscle waste are critical elements of therapy,” the study said.

“In agreement with previously published data, swim training significantly decreases the reduction in muscle strength clearly visible at the symptomatic stage of ALS, . . . reduces oxidative stress, and improves muscle energy metabolism at terminal stage of the disease,” the researchers stated.

“Our findings indicate that swim training is a modulator of skeletal muscle energy metabolism with concomitant improvement of skeletal muscle function in ALS mice,” they concluded.

Here is the link to the report on the study:

Monday, January 21, 2019

Impaired Nuclear Export of Polyglutamine-Expanded Androgen Receptor in SBMA

The link below is to a very detailed report on a recent Kennedy's Disease (SBMA) research study. It is too detailed for me to summarize.

Impaired Nuclear Export of Polyglutamine-Expanded Androgen Receptor in Spinal and Bulbar Muscular Atrophy


... It has been widely reported that the ligand-dependent nuclear accumulation of mutant AR is required for SBMA pathogenesis17,18,46. This mechanistic insight into the toxicity of polyQ-expanded AR ultimately led to clinical studies that tested the effect of the androgen suppressors leuprorelin acetate and dutasteride on disease progression in SBMA patients81,82,83. Despite recent evidence that long-term treatment with leuprorelin acetate modestly slows disease progression84, overall the protective effects of androgen suppressors observed in SBMA animal models have not had a substantial impact on disease progression in symptomatic patients. The lack of an effective treatment for SBMA underscores the need for a better mechanistic understanding of aspects of mutant AR metabolism that can be targeted to ameliorate its toxic effects. To this end, the goal of this study was to determine if nuclear export, a poorly understood step in the metabolism of AR, plays a role in SBMA pathogenesis and whether reducing nuclear AR by enhancing its export can reduce its aggregation and toxicity.

The results of our study demonstrate (1) that the nuclear export of polyQ-expanded AR is impaired, (2) that enhancing the nuclear export of polyQ-expanded AR with an exogenous NES decreases its aggregation and toxicity by promoting its proteasomal degradation, (3) that polyQ-expanded AR exhibits reduced phosphorylation at S650 and that blocking S650 phosphorylation further exacerbates its nuclear export deficiency, and (4) that global disruption of nucleo/cytoplasmic transport is not a common feature of SBMA models.  ...

...  This study offers the first evidence that the nuclear export of polyQ-expanded AR is impaired, highlighting a novel aspect of AR metabolism that may contribute to the pathogenesis of SBMA. Furthermore, our data support a model in which the mutant AR is rapidly degraded by the proteasome once exported from the nucleus, thereby decreasing its stability, aggregation, and toxicity. Although additional work will be required to fully elucidate the mechanism underlying deficient nuclear export of polyQ-expanded AR, our results provide a new direction for investigations into therapeutic manipulation of the mutant, polyQ-expanded AR in SBMA.

Monday, January 14, 2019

Using Exercise and Other Physical Therapy Interventions to Optimize Functional Mobility

Below is a link to a PDF that was used for a presentation at the KDA annual conference. Anyone who follows my blog knows that I highly recommend developing a frequent and sustainable "smart" exercise program for those of us living with Kennedy's Disease (SBMA). The presentation expounds upon the benefits of a regular exercise program as well as provides warnings and tips.

As always, I recommend three things:
1. Consult with your doctor and a physical therapist before beginning any exercise program.
2. A PT familiar with KD or ALS is essential in the design of a sustainable program.
3. Don't overdo. Listen to your body.

Using Exercise and Other Physical Therapy Interventions to Optimize Functional Mobility

Joseph Shrader, PT, CPed

Click on this link to see some other presentations that given at the annual conference.

Friday, January 11, 2019

Patient trial shows impressive clinical results

The following article is from The Florey. A few people have commented that this might be helpful for Kennedy's Disease, SBMA. I am not an expert, but KD impacts the lower motor neurons. Lung function and cognitive ability are not normally affected. ALS is both an upper and lower motor neurons disorder. Lungs are affected. The drug trial mentioned appears to help upper motor neurons.

Motor neurone disease breakthrough: Patient trial shows impressive clinical results

A new drug delays motor neurone disease progression and improves cognitive and clinical symptoms. The latest trial results were announced by a spin-out company from the Florey and University of Melbourne, Collaborative Medicinal Developments.

Research at a glance:

The copper-delivery drug CuATSM improved symptoms in MND patients over six months
Improvements were seen in lung function and cognition. Decline in motor disability was reduced in treated patients compared to standard-of-care patients. The researchers will begin a larger Phase 2 trial to confirm CuATSM’s effectiveness in motor neurone disease. 

A new drug developed by scientists at the Florey Institute of Neuroscience, and the School of Chemistry and Bio21 Institute at the University of Melbourne has dramatically improved clinical and cognitive symptoms of motor neurone disease, also called amyotrophic lateral sclerosis.

This is the first human evidence for a disease-modifying drug for motor neurone disease. It is a huge breakthrough, and we look forward to confirming the positive results in a larger study soon

Motor neurone disease is a progressive, fatal neurodegenerative disease. Its key hallmark is the death of the brain cells that control muscle movements. This results in muscle weakness and eventually paralysis. Patients usually die of respiratory failure within three years of diagnosis, and there are no treatments or disease-modifying therapies available.

In this dose-finding trial involving 32 patients, the group given the highest amount of the CuATSM compound showed improved lung function and cognitive ability, compared to the predicted declines observed in standard-of-care patients. Further, treated patients showed a much slower overall disease progression as measured by a global disability score.

Professor Ashley Bush, Chief Scientific Officer of Collaborative Medicinal Development and director of the Melbourne Dementia Research Centre, said “This is the first human evidence for a disease-modifying drug for motor neurone disease. It is a huge breakthrough, and we look forward to confirming the positive results in a larger study soon.” 

Associate Professor Kevin Barnham of the Florey, Associate Professor Anthony White at the Queensland Institute of Medical Research, and Professor Paul Donnelly and Associate Professor Peter Crouch from the University of Melbourne, developed and tested CuATSM over a 15-year period. After showing its therapeutic potential for motor neurone disease in pre-clinical models, the researchers founded a company, Collaborative Medicinal Development, to take the drug into human studies. 

Professor Donnelly said, “It is gratifying to see such promising results made possible by collaborative fundamental research at the interface between chemistry and biology.” The results were reported at the 29th International Symposium on ALS/MND in Glasgow by Dr Craig Rosenfeld, CEO of Collaborative Medicinal Development.

The researchers plan to begin enrollment for a larger, randomised, placebo-controlled double-blind Phase 2 trial in mid- to late 2019. This trial will test CuATSM’s effectiveness in motor neurone disease / amyotrophic lateral sclerosis in a larger patient sample.