Among presentations at the April event, were ALS focused studies conducted by Dr. Sara van Mossevelde, Dr. Adriano Chio, Dr. Lindsey Hayes, Dr. Teresa Jacobs, Dr. Jeremy Shefner and Wendy Kaye.
Mossevelde, from the University of Antwerp, in Belgium, presented evidence that the C9orf72 gene mutation exhibits a phenomenon known as “anticipation” – when a disease starts earlier in life from the previous generation.
Her team studied the clinical characteristics of 29 families with the mutation and found that the youngest generations had disease onset an average of seven years before their grandparents. The surprising results also showed that the duration of the disease was not very different between generations compared to the frequently observed pattern of more severe progressions in diseases that also shown anticipation. Next, the team will attempt to find reasons for the difference.
Chio, from the University of Torino, in Italy, presented data on the influence of the APOE gene on the cognitive features of ALS patients. APOE is found prominently in Alzheimer’s disease, where the possession of the APOE2 allele (variant gene) is linked to a reduced risk of dementia.
Chio’s groundbreaking research found that the opposite is true for ALS. People carrying the APOE2 allele had 2.5 times increased risk of dementia when compared to those not carrying the allele. The future of this research includes investigation to find the reason for the difference between ALS and Alzheimer’s.
Hayes from Johns Hopkins University, in Baltimore, Md., presented work showing that tracking one of the C9orf72-produced proteins could provide a good biomarker for response to therapy against the mutation.
C9orf72 is the most common genetic cause of ALS. The mutation is responsible for the production of dipeptide repeat proteins (DPRs) — small proteins composed of two repeating amino acids. Hayes and her team found that the level of one DPR escalated according to dose increases of an antisense treatment against the C9orf72 mutation, suggesting that measuring this CPR might be useful in clinical trials. Further work will include validation.
Jacobs, from the University of Michigan in Ann Arbor, Mich., conducted a pilot study with colleagues suggesting that initiating non-invasive ventilation (NIV) before it is necessary might bring more benefits than waiting in ALS patients.
The team used a novel trial design, in which ALS patients with a forced vital capacity (FVC) measure of respiratory function, above 50% of what was predicted, were randomized to receive either active NIV or sham NIV. The FCV of those receiving active treatment declined slower than those who received sham treatment.
“This trend toward improved respiratory function seen in this pilot trial warrants further study of early NIV therapy in ALS,” Jacobs said in a press release.
Shefner, from the Barrow Neurologic Institute in Phoenix, Az., with a team of colleagues presented data showing that changes in slow vital capacity (SVC) respiratory measure, predicted changes in further measures of ALS decline – including the need for invasive ventilation and risk of death.
The team’s results are significant for the interpretation of clinical trial results, specifically tirasemtiv, a drug shown to slow SVC decline in ALS patients. A Phase III clinical trial (VITALITY-ALS) began last July 2015 to test tirasemtiv. A change in SVC will be a primary outcome measure to determine the drug’s symptomatic effect on ALS.
In addition, Wendy Kaye and colleagues, from the National ALS Registry headed a presentation on the feasibility of a national biorepository of ALS biospecimens, including tissue and body fluids. The national biorepository will likely launch in the fall of 2016.