Long term treatment of Huntington disease with L‐glutamate and pyridoxine

Abstract

Decreased levels of gamma aminobutyric acid (GABA) and its synthetic enzyme, glutamic acid decarboxylase, have been found in the brains of patients with Huntington disease. In an attempt to augment GABA-mediated neurotransmission, daily doses of 25 gm of L-glutamate (the substrate for glutamic acid decarboxylase) and 500 mg of pyridoxine, its cofactor, were given to five patients with Huntington disease. This regimen was continued for 2 years. Assessment of motor and behavioral function indicated no improvement on this regimen.

Non-nutritional uses of vitamin B6

“…Supplements of vitamin B 6 ranging from 25 to 500 mg/d have been recommended for treatment of a variety of conditions, discussed later, in which there is an underlying physiological or biochemical mechanism to justify the use of supplements, although in most cases there is little evidence of efficacy. It has also been used empirically, with little or no evidence of efficacy, in the treatment of a variety of conditions, including: acute alcohol intoxication (Mardel et al 1994), atopic dermatitis (Mabin et al 1995), autism (Rimland et al 1978;Rimland, 1988;Lelord et al 1982;Pfeiffer et al 1995;Findling et al 1997), dental caries (Hillman, 1964), diabetic peripheral neuropathy (Levin et al 1981;Cohen et al 1984), Down's syndrome (Pueschel et al 1980;Coleman et al 1985), Huntington's chorea (Barr et al 1978), schizophrenia (Bucci, 1973), and steroiddependent asthma (Sur et al 1993).…”

Pharmacological Management of Huntingtons Disease: An Evidence- Based Review

“…Also valproate, which is thought to elevate brain GABA levels, had no beneficial effect on involuntary movements in two case reports [146,147]. In an attempt to augment GABA-mediated neurotransmission, L-glutamate (the substrate for glutamic acid decarboxylase) and pyridoxine, its cofactor, were given in an open label trial to five patients for two years without motor or behavioral effect [148].Interestingly, levetiracetam markedly reduced chorea, but induced parkinsonism and lethargy in a HD patient [149].…”

Neuroprotection in Huntington;s Disease

“…Also valproate [34], which is thought to elevate brain *Address correspondence to this author at the University Clinic of Psychiatry, Graz Medical University, Auenbruggerplatz GABA levels, had no beneficial effect on involuntary movements in three HD patients. In an attempt to augment GABA-mediated neurotransmission, L-glutamate (the substrate for glutamic acid decarboxylase) and pyridoxine, its cofactor, were given in an open label trial to five patients for 2 years without motor or behavioural effect [35], Benzodiazepines act at the GABA-benzoacepine receptor complex in the brain to enhance GABA action, possess anxiolytic, sedative, hypnotic and anticonvulsant properties [36] and may therefore afford nonspecific suppression in HD patients. Reisine et al [37] have stated that the degeneration of striatal neurons and the associated loss of benzodiazepine receptors are central to the understanding of the neurochemistry of HD.…”