D-Cycloserine:

A Novel Treatment for

Gulf War Illness
Rosemary Toomey, Ph.D
toomey@bu.edu

D-Cycloserine (DCS)

It is an FDA approved antibiotic used to treat tuberculosis

at high doses; i.e. 500 mg daily.

It is a small molecule, able to cross the blood brain barrier.

Thus, it is active in the central nervous system.

It binds to the glutamatergic N-methyl-D-aspartate (NMDA)

receptor

D-Cycloserine (DCS)

Glutamate is an excitatory neurotransmitter that is involved in

learning, memory functioning, and general cognition.

There is too much glutamate in disorders such as Alzheimer's

disease, Parkinsons disease, and amyotrophic lateral sclerosis
(ALS).

In animal models of chronic illnesses, DCS normalizes glutamate

levels.
Reduces
Memory deficits

Neuroinflammation (Brain inflammation)

Nerve cell death in the hippocampus

Cognitive Enhancement
Acute dosing: Single doses or weekly doses of 50-250 mg.

Successful use of DCS to treat anxiety disorders when used

together with Cognitive Behavior Therapy. It improves learning
and memory and reduces fear and anxiety.
Hofmann (2014)

Some effects were also seen in persons without anxiety, where

DCS improves performance on non-emotional memory tasks
(e.g., recalling novel word lists each week).
Otto et al. (2009)

In non-anxious people, DCS improved procedural learning, or

learning how to do things (motor skills).
Kuriyama et al. (2011)

Anti-inflammatory (Neuroinflammation)
Chronic Dosing: Daily treatment of 50-100 mg for a month.

Alzheimers Disease: Improvement in cognition.

Tsai et al., 1999

Schizophrenia: Improvement in negative symptoms, memory

consolidation, and delusions when combined with CBT.
Goff, 2012

Treatment-resistant Major Depression: Improvement in depression

symptoms.
Heresco-Levy, 2013

Autism spectrum disorder: Improvement in sociability and reduction

in stereotypic/repetitive movements.
Urbano et al., 2014

Why it may be useful in GWI

Gulf War Illness is a multi-symptom illness.

GWI Consortium is focusing on the role of neuroinflammation

in this condition.

Neurotoxicant exposure triggers an immune system reaction

resulting in neuroinflammation and cognitive symptoms.

DCS works here

Neurotoxicants
Pesticides, Sarin,
Agent Orange,
PB pills, anthrax
vaccine, etc.

Neuroinflammatio
n
Measured by the
presence of proinflammatory
cytokines (CRP,
TNF, IL-1)

Cognitive
Symptoms
Diminished
short-term
memory, poor
attention,
worsened mood

Study Design

Main Intervention:
DCS medication, self-administration
100 mg daily for one month

2 groups of subjects:
Experimental Group: DCS Medication
Control Group: Placebo

Double Blind Study Design

Participant and examiner will not know who is taking DCS.

Assessments:
GWI symptoms, neuropsychological test performance, mood,
sleep, quality of life.

Study Goals and Timeline

Goals:

Is DCS safe in GW veterans?

Does DCS improve cognition?
When in the month do you see that improvement?

Timeline of Study:
6 visits over about two months.
Visits starting in June 2016.

Thank you!

Thank you for your service!