Our Knoxville ALS Support group was fortunate to hear a presentation, “Bases Loaded: Poised for the Next Strike Against Lou Gehrig’s Disease”, by Richard S. Bedlack MD PhD FAAN,DukeUniversityat our past meeting on January 18, 2012. The overview of the presentation covered, History lesson, Progress since Lou Gehrig, Why don’t we have a cure yet?, How we are “loading the bases”, and Where might the “Next Strike” come from.
ALS (Amyotrophic Lateral Sclerosis) was known of in the medical word as early as 1874. It was given the name Lou Gehrig’s Disease for the well-know Yankee baseball player who let the world become familiar with this disease from which he passed away from in 1939. ALS attacks both the upper and lower motor neurons.
Progress since Lou Gehrig:
Multi-Disciplinary Clinics have been set in place to help prolong survival, and preserve quality of live. Medications are given to help with drooling, pseudo bulbar affect, pain, shortness of breath, constipation, insomnia, and depression. One FDA approved medication prescribed is Riluzole, which prolongs survival a few months, but does not affect the quality of life. Equipment such as power chairs, lifts, beds, speech generating devices, feeding tubes, spinal pumps, cough assist, percussion vests, non-invasive and invasive ventilators have been very helpful to patients. The FDA HUD approved a Diaphragm Pacing System in 2011 for carefully selected patients. The efficacy is still unclear. It is said to slow decline in FVC, prolong tracheotomy-free survival and improve sleep, but the data is highly flawed thus far. Eye gaze systems have also been helpful to patients to communicate and run devises. Clinical trials are in process constantly.
Why don’t we have a cure yet?
Diagnosis takes too long. Usually it takes 14 months from symptom onset to diagnosis. 50% of the motor neurons are lost during this timeframe.
How we are “loading the bases?
Dr. Bedlack stated that research is on the cusp of diagnosing biomarkers which will help doctors make a diagnosis faster and more accurate. Proteomics are revolutionizing search. The second Pasinetti study is currently underway in which they are looking into a SELDI Protein Chip Technology hoping to replicate the results from the first study. Electro physiologic Candidates: “The Million Dollar Baby” is a way of measuring diseased muscle through a set of four electrodes applied to the skin which can measure muscle deterioration caused by ALS. The rate of gene discovery in ALS is increasing. The summer of 2011, UBQLN2 and C9irf72 two of the newest genes were found of the 22 that cause familiar ALS.
Research is also looking into disease origins. There are two types of ALS, Familial ALS and Sporadic ALS. Two studies are being done on susceptibility genes. They are also looking at exposures such as toxins, athleticism, smoking, high fat diets and trauma.
A big way to get government support ($) for ALS research is through all patients enrolling on the National ALS Registry, www.cdc.gov/als or by calling (800) 232-4636. Through this registry not only will ALS research receive funds, but they can also investigate clusters of registered ALS patients throughout the world.
Research has shown that the ALS is not due to the SOD1 protein deficiency. SOD1 gets rid of free radicals. In ALS the SOD1 gains a toxic function. Mutations in the SOD1 impair multiple cell functions. Through their research they are finding that Protein is the problem, not the lack of it. Research is finding an emerging theme; events occurring outside the motor neuron may play a major role.
Where will the next strike come from?
A rich pipeline of new candidate therapies is emerging: new mechanisms, high throughout drug screening and novel attach strategies including drugs attached to viral vectors, gene therapy, Antisense Oligos/RNA interference, and stem cells.
Stem cell is the only therapy that might be able to restore lost function, but questions remain yet unknown such as: the source, the amount, the location, do they replace glial cells or neurons, and are additional meds needed. In the USA, Neuralstem (www.neuralstem.com) has FDA approval for a pilot trial in American ALS patients. The pilot trial was at Emery in January of 2010. 12 total patients transplanted so far; no obvious harm; 8 surviving patients seem to have improved progression rates of which 1 of the 8 is getting stronger. This is very exciting news! BEWARE OF FRAUDS! Google, 20/20, “21st Century Snake Oil”. Also go to www.ALSUntangled.com to check on myths.
Symptom management has improved markedly; PALS are living better and longer than ever before.
There is still no markedly effective disease modifying therapy. However, gains in diagnosing and understanding the disease are “loading the bases” for something big.
We have a rich pipeline of therapeutic candidates in trials and may soon be able to slow ALS more effectively. The next generation of therapy may even be able to reverse it.