Theme 2 Genetics and genomics.

Area of Science:

• Neurology
• Genetics
• Personalized Medicine

Background:

• Genetic factors contribute to a significant portion of ALS cases, driving the need for gene-targeted therapies.
• Current ALS management guidelines lack recommendations for genetic testing, creating barriers for patients seeking diagnosis.
• The ALS GAP program was established to provide genetic testing for ALS patients with a family history of ALS or dementia.

Purpose of the Study:

• To establish a pilot program for ALS genetic testing within NEALS clinics.
• To determine the rate of ALS gene identification in a US clinic-based patient population.

Main Methods:

• The ALS GAP program offers genetic testing to ALS patients with a family history of ALS (fALS) or dementia (dALS) at participating NEALS clinics.
• fALS patients are eligible for C9orf72 testing, with an option to expand to a five-gene panel (SOD1, FUS, TARDBP, TBK1, VCP).
• dALS patients are eligible for C9orf72 testing only.

Main Results:

• 29.5% of US NEALS clinics participated in the pilot program.
• Out of 142 patients tested, 54.9% were fALS and 45.1% were dALS.
• Genetic variants were identified in 53.9% of fALS cases and 20% of dALS cases, with C9orf72 being the most common finding.

Conclusions:

• The ALS GAP program demonstrates significant interest in genetic testing among ALS clinicians and patients.
• The program addresses barriers such as cost and appropriate test selection, though gene identification rates in fALS may be lower than in research cohorts.
• This pilot program can serve as a model for clinical ALS genetic testing, emphasizing the need for consistent policies and understanding of clinic-based population genetics.