- Immune misregulation may be a common endpoint of various pathways that damage the nervous system in ALS.
- Mice that received treatment to combat a misfolded and toxic protein showed benefit, bolstering support for this type of therapy for ALS.
- Clinical trials in ALS patients of strategies that use stem cells to repair or replace damaged cells are continuing.
- A trial of a drug that may improve muscle function in ALS patients is continuing, with results expected in spring 2014.
"We are undoubtedly slowing down the MND [motor neuron disease] supertanker, and can start to see how we might turn it around for the first tim," said Martin Turner, senior clinician scientist at the University of Oxford (United Kingdom), on research being reported on at the 24th International Symposium on ALS/MND.
The symposium, held Dec. 6-8, 2013, in Milan, Italy, included more than 950 people from 34 countries, who gathered to hear the latest findings from scientific and clinical experts in amyotrophic lateral sclerosis (ALS), often referred to as "motor neuron disease" (MND) in the United Kingdom.
Jane Larkindale, MDA's vice president of research, attended the conference and was encouraged by progress in several areas of therapeutic development. "This was an exciting meeting," she says. "There were nearly a thousand ALS experts in one place, talking about little else than what the barriers are to understanding and treating ALS, and how to overcome those barriers."
Four areas covered at the conference were:
- modulating the immune system;
- combatting buildup of toxic protein or RNA;
- supplying new cells to help compensate for degeneration in the nervous system; and
- improving muscle function despite nervous system damage.
Stanley Appel, a meeting participant from Methodist Neurological Institute in Houston and a longtime MDA research grantee, commented that several of the mechanisms found to underlie ALS appear to converge on misregulation of the immune system, an area of great interest to him.
Among the immune system modulation strategies for ALS now in development are:
- IMS-088, an experimental compound that targets a key inflammatory pathway;
- a five-drug regimen used to suppress the immune system in people who participated in a recent stem cell trial that might have neuroprotective effects;
- fingolimod (Gilenya), a drug that dampens the immune response and is used for the treatment of some forms of multiple sclerosis; and
- NP001, an experimental compound that targets immune system cells, causing them to switch from an "attack" to a "protective" mode.
Combatting toxic proteins and RNA
Meeting participant Jan Grimm, chief scientific officer at the Swiss company Neurimmune, described how mice that received antibodies (proteins made by the immune system) against a misfolded, toxic protein known to cause ALS showed improvements in gait and the distance they walked, as well as longer survival and fewer abnormal protein clumps in their cells.
Additional strategies being pursued to combat toxic proteins and RNA are:
Replacing or repairing damaged cells
Meeting participant Dimitrios Karussis of Hadassah Medical Center in Jerusalem, who is testing the effects of bone marrow-derived, NurOwn stem cells in ALS patients in a clinical trial, said current trials have shown these cells are apparently safe and well-tolerated. Plans are to increase the dosage.
Among the strategies being pursued to support existing nerve cells or supply new ones are:
Improving muscle function
Investigators testing the drug tirasemtiv, which may increase muscle sensitivity to signals from the nervous system, said they hope to have results in spring 2014.
Tirasemtiv was found safe and well-tolerated in an earlier study, the results of which were published in August 2013. The drug is now in a phase 2b, 400-person trial in people with ALS.