Why Aren’t There Good Drugs for Autism? Ex-MDRNA Exec Takes a Shot at Pharma’s Neglected Disease

[Guest guest]

Why Aren’t There Good Drugs for Autism? Ex-MDRNA Exec Takes a Shot at Pharma’s Neglected Disease

http://www.xconomy.com/seattle/2009/09/14/why-arent-there-good-drugs-for-autism-ex-mdrna-exec-takes-a-shot-at-pharmas-neglected-disease/

Luke Timmerman 9/14/09

[Corrected: 09/14/09, 12:40 pm. See below.] Autism has stumped drug developers for a long time. Scientists say they don’t really know what causes it. There’s a long list of symptoms, from social isolation, to obsessive behaviors like staring at ceiling fans, to difficulty with language. So it’s hard for drug developers to form a strategy to treat this disease, and not surprisingly, the condition doesn’t rank high on the research agendas of most drug companies.

That was true at Bothell, WA-based Nastech Pharmaceuticals (now called MDRNA), which long had a project on the back burner that held some promise for autism. When the company did some major downsizing a year ago to conserve cash, president Gordon Brandt was let go, and negotiated to take that neglected piece of intellectual property with him. That license has now formed into a business plan for a company Brandt is calling Anatrope Pharmaceuticals, which he told me about the other day at a Starbucks near Xconomy’s office.

“This always rattled around as number 4 on our priority list at Nastech, and never really got the attention it deserved,†Brandt says.

Autism has been riding a wave of increased public awareness, and is now said to affect about one out of every 150 kids in the U.S. Celebrities like McCarthy have pushed the idea that preservatives in childhood vaccines are causing the rising incidence, although scientists say there isn’t convincing data to support this. Yet despite all this popular attention (Bruce Springsteen and Jerry Seinfeld are scheduled to headline a fundraiser for Autism Speaks, a patient advocacy group, in New York on Nov. 17), there’s been surprisingly little progress, or competition, in the biotech and pharma industries to create effective new therapies. Right now, some children with irritability from autism get atypical antipsychotics like & ’s risperidone (Risperdal), or depression meds, but behavioral therapy appears to be the best option for kids diagnosed with autism, Brandt says.

The idea at Anatrope is to build on research into oxytocin, the “hormone of bonding and trust,†as Brandt puts it. Levels of oxytocin spike for both mothers and their babies during breastfeeding; the hormone is supposed to play a role in the bonding process. [Editor's note: Previous sentence revised to clarify role of oxytocin in breastfeeding]. A 2005 paper in Nature lent more credence to this concept of bonding and trust, by showing

that adult subjects given oxytocin were more willing to trust financial advisors with their money, Brandt says.

Since one of the main symptoms of autism is social isolation and lack of ability to empathize with other people’s emotions, it was hypothesized that oxytocin might be a decent drug candidate, Brandt says. The problem is it’s hard to deliver in drug form, because it only lasts in the bloodstream for a few minutes. That’s why his former company worked on carbetocin, a similar peptide molecule that can last four hours in the body instead of about four minutes, Brandt says. Carbetocin has been made into a nasal spray form, which could provide convenient dosing.

No other company has a drug like this in clinical trials, and Brandt says his research can find only three other competitors testing the clinical effects of their drugs on patients with autism. Bristol-Myers Squibb and Takeda Pharmaceuticals are testing a new use of aripaprazole (Abilify) for the severe irritability of some autism patients, BioMarin has a small trial of sapropterin (Kuvan), and Neuropharm failed earlier this year in a pivotal trial of generic, low-dose form of fluoxetine (Prozac).

Nastech had already done the work formulating carbetocin into a drug, ran it through animal studies, and got the drug candidate to the point where Anatrope can start a mid-stage clinical trial to demonstrate whether it works in people, before it was shelved. The challenge for Brandt is raising at least $5 million to run that trial.

Even though the Anatrope drug is further along in development than many of the other therapies venture capitalists typically invest in, Brandt says he’s run into a lot of VCs who don’t know anything about autism, and seem too preoccupied with propping up their existing portfolios to think about making new investments. (That didn’t surprise me much, but I was surprised to hear Brandt say that unlike patient advocacy groups for other conditions like cystic fibrosis or muscular dystrophy, autism foundations are full of highly motivated parents, yet they don’t appear to have much money for clinical trials.)

Brandt is collaborating on the company with Hollander, a psychiatry researcher at Albert Einstein College of Medicine in New York, and three other people he worked with previously at Nastech who are familiar with the autism program. [Correction: an earlier version of the story included an outdated affiliation for Hollander.] The team has the outline of a clinical trial design in hand—a high and a low dose, placebo-controlled, 90 patients in the U.S., four weeks of observation, and a budget of $5 million. “It’s a gigantic potential market, there’s nothing out there for it, and it takes little money,†to run such a small trial, Brandt says.

It’s unclear whether Brandt can raise the cash he needs or not, but I got the sense he’s really passionate about taking the program forward. He doesn’t have a child with autism, but he’s gotten intense support from those who do.

I saw it firsthand the morning we met at Starbucks. A woman sitting at a nearby table overheard our interview, and after about 45 minutes, she stood up and introduced herself to Brandt. She flipped open her cell phone, showed it to him, and said, “This is a picture of my daughter. She has autism. Keep up the good work.â€

That sort of random support, Brandt says, is part of what keeps him knocking on VCs doors to get Anatrope off the ground. “I jump out of bed excited each morning,†he says.

Luke Timmerman is the National Biotechnology Editor for Xconomy. You can e-mail him at ltimmerman@..., call , or follow him on Twitter at http://twitter.com/ldtimmerman

Lin Wessels

Sam's MAMA

(Mom on A Mission for Autism)Our Lives Begin To End The Day We Become Silent About Things that Matter. ~ Luther King