Determining the Safety of L-serine in ALS

Phoenix Neurological Associates, LTD

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Amyotrophic Lateral Sclerosis (ALS)

Treatments: Drug: L-Serine

Study type: Interventional

Funder types: Other

Identifiers

NCT01835782

L-Serine2013

IND (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to determine the safety of L-Serine in subjects with Amyotrophic Lateral Sclerosis (ALS) at varied doses.

Full description

Previous studies into the Guamian ALS-Parkinson's Dementia complex has identified β-methylamino-L-alanine (BMAA), as a potential neurotoxin responsible for this disease. BMAA is a non-essential amino acid and is produced by a cyanobacterium which is present in all ecosystems. Subsequently several groups have identified high concentrations of BMAA in brain tissues of patients from North America and Europe with several neurodegenerative diseases including ALS, Parkinson's Disease and Alzheimer's Diseases. It has been hypothesized that chronic intake of BMAA in the diet leads to mis-incorporation of the amino acid into brain proteins, where it produces slow neuronal damage and recent evidence has shown that BMAA is mis-incorporated into proteins in neuronal cell lines via seryl tRNA synthetase, thereby producing protein mis-folding and protein aggregates, leading to cell death. It has been demonstrated in mammalian neuronal cell cultures that exogenous L-serine could prevent the BMAA neurotoxin from being mis-incorporated into proteins, thereby preventing cell death and that very high doses of L-serine may compete with the transport of a number of non-essential amino acids across the blood-brain barrier via the y+ transporter. These findings have led us to believe that high doses of L-serine could possibly stop the mis-incorporation of BMAA into brain proteins which in turn would slow or even abate the progression of ALS. This study will determine the safety of different doses of L-serine given to ALS subjects at 0.5 gm twice daily (BID), 2.5gm BID, 7.5g BID or 15 grams BID for six months.

Enrollment: 20 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age 18-85
2. Male or Female
3. Clinically diagnosed with probable or definite ALS based on El Escorial criteria
4. ALSFRS-R > 25
5. Able to provide informed consent to and comply with all medical procedures

Exclusion criteria

1. Outside age range of 18-85
2. Subjects with forced vital capacity (FVC) below 60%
3. Evidence of any motor neuron disease for over 3 years

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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20 participants in 4 patient groups

2.5 grams BID

Active Comparator group

Description:

5 Patients will be evenly randomized into this group

Treatment:

Drug: L-Serine

.5 grams BID

Active Comparator group

Description:

5 Patients will be evenly randomized into this group

Treatment:

Drug: L-Serine

7.5 grams BID

Active Comparator group

Description:

5 Patients will be evenly randomized into this group

Treatment:

Drug: L-Serine

15 grams BID

Active Comparator group

Description:

5 Patients will be evenly randomized into this group

Treatment:

Drug: L-Serine