Clinical Manifestations and Biomarkers in Amyotrophic Lateral Sclerosis Type 4 and Other Inherited Neurological Disorders of RNA Processing

Conditions

• Amyotrophic Lateral Sclerosis Type 4
• Inherited Neurological Disorders of RNA Processing

Eligibility Criteria

Sex

ALL

Age

5 Years - 120 Years

Healthy Volunteers

Accepted

Study Details

Background: Amyotrophic lateral sclerosis type 4 (ALS4) is an inherited motor neuron disease. People with ALS4 have a change in the amount of RNA and DNA that bind together. This binding of RNA with DNA forms units called R-loops. Researchers want to learn how R-loops are related to ALS4. To do this, they will study people with inherited neurological conditions that may affect R-loop levels. These include ALS4, progressive external opthalmoplegia with mitochondrial deletions (PEOB2), Aicardi-Goutieres syndrome (AGS), and ataxia and oculomotor apraxia type 2 (AOA2). Objective: To learn how the binding of RNA with DNA (R-loops) is related to neurological disease. Eligibility: People age 5 and older with ALS4, PEOB2, AGS, and AOA2. Healthy relatives and nonrelatives are also needed. Design: Participants may be screened with a review of x-rays and other medical records. Healthy relative and nonrelative participants will have 1 visit. All other participants will have 4 visits over 3 years. At visits, participants will undergo some or all of the following: Medical history Physical exam Tests of muscle strength and volume and physical function Blood tests Pregnancy test (for some females) Skin biopsy of forearm Magnetic resonance imaging (MRI) Dual x-ray absorptiometry (DEXA). Some tests are optional. The MRI uses a magnetic field and radio waves to take pictures. Participants will lie on a table that slides in and out of the scanner. The scanner makes noise. They will get earplugs. The DEXA scan uses x-rays to take pictures. MRI and DEXA will be used to measure muscle, fat, and lean body mass. ...

Key Dates

Start date

Dec 14, 2020

Status verified

Nov 2025

Primary completion

Dec 25, 2030

Completion

Dec 31, 2030

Study Design

Enrollment

330 participants (estimated)

Arms

• Arm: ALS4 Patients
  Patients with ALS4 inherited defect in the senataxin (SETX) gene.
• Arm: Disease Control Participants
  Disease control participants with mutation in other genes which alter RNA processing (e.g., RNASEH1+2 and loss of function SETX mutations in patients with ataxia and oculomotor apraxia type 2\[AOA2\]).
• Arm: Gain of Function
  patients with gain of function mutations in genes that result in other forms of neurological disease, as well as select patients with mutation in the SETX gene (select ALS4 patients), will be enrolled and followed annuallt for 5 years.
• Arm: Related, Unaffected Healthy Controls
  Unrelated, unaffected healthy relatives of the ALS4 and disease control groups enrolled as controls.
• Arm: Unrelated, Healthy Controls
  Unrelated, healthy volunteers who are age and sex matched to the affected ALS4 and disease control participants.

Primary Outcome Measure

Disease progression as measured by thigh muscle volume and other study measures [ Time Frame: Baseline and annually at visits 2 - 4 ]

Central Contacts

• Angela D Kokkinis, R.N.
  (301) 451-8146
  [email protected]
• Christopher Grunseich, M.D.
  (301) 402-5423
  [email protected]

Locations (1)

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