(Adds detail about GSK in paragraph 3)

By Nancy Lapid

Sept 23 (Reuters) - On Monday, the U.S. Food and Drug

Administration published a notice to the Federal Register ahead

of a speech by President Donald Trump, approving a version of

leucovorin made by GlaxoSmithKline that the company had

previously withdrawn from the FDA's consideration when it

stopped manufacturing the drug.

The FDA cited a review of the use of leucovorin in 40

patients with a rare metabolic disorder called cerebral folate

deficiency that can lead to a range of neurological symptoms,

some of which are seen in people with autism.

GSK stopped manufacturing and marketing its version of

leucovorin in 1997 but still holds the New Drug Application

(NDA), meaning it is responsible for requesting new indications

to be added.

It said on Monday

it would, at the request of the U.S. FDA, submit an

application to update the label to include an indication for the

treatment of cerebral folate deficiency.

Here's what is known about leucovorin and autism.

WHAT IS LEUCOVORIN?

Leucovorin, also known as folinic acid, is a form of folate,

an essential B vitamin, or B9.

Leucovorin has been approved by the U.S. Food and Drug

Administration for counteracting the toxic effects of certain

cancer drugs, like methotrexate, that block the body's use of

folate.

Leucovorin is also used to enhance the effects of other

chemotherapy drugs and to treat specific types of anemia. The

drug can be given orally or intravenously.

It is made by more than half a dozen companies, according to

the U.S. Food and Drug Administration website.

WHY IS FOLATE IMPORTANT?

Folate helps cells grow and divide. It also supports the

immune system and helps produce healthy red blood cells. In

developing fetuses, inadequate folate leads to a type of serious

birth defect called neural tube defects.

The U.S. Centers for Disease Control and Prevention advises

all women capable of becoming pregnant to supplement their diet

with 400 mcg of folic acid every day to help prevent neural tube

defects.

Some studies, but not all, have also found an association of

low maternal folate levels during early pregnancy with an

increased risk of autism in children.

WHY CONSIDER USING LEUCOVORIN TO TREAT AUTISM?

Doctors have been prescribing leucovorin for autism

off-label, or repurposing a drug approved for one condition to

treat another.

Studies from researchers at SUNY Downstate Medical Center in

Brooklyn, New York, and elsewhere have suggested that up to

three-fourths of children with autism have genetic variations

that impair their body's ability to process folate or autoimmune

disorders that block folate transport to the brain.

Other small studies have linked these findings with more

severe forms of the disorder and suggested that treatment with

leucovorin can improve verbal skills, social skills and

irritability in these youngsters.

However, the science regarding leucovorin and autism "is

still in very early stages, and more studies are necessary

before a definitive conclusion can be reached," the Autism

Science Foundation said in a statement.

The data in favor of treatment with leucovorin is "from four

small randomized controlled trials, all using different doses

and different outcomes, and in one case, reliant on a specific

genetic variant," the Foundation notes on its website.

Dr. David Mandell, a professor of psychiatry and autism

expert at the University of Pennsylvania, told Reuters that

leucovorin might well be a possible treatment for some children

with autism, "but the evidence we have supporting it... is

really, really weak."