Stories about: Therapeutics

Dually-targeted liposomes curb triple-negative breast cancer, metastases in mice

dual targeting for triple-negative breast cancer
(IMAGE: ADOBE STOCK)

Some 15 to 20 percent of all breast cancers are triple-negative, meaning they lack receptors for estrogen, progesterone and human epidermal growth factor type 2. They have the worst prognosis of all breast cancers and very limited treatment options. Finding a treatment that distinguishes between cancer cells and normal cells has been especially challenging.

A novel precision medicine strategy described today in Science Advances offers an intriguing ray of hope. Researchers at Boston Children’s Hospital, with bioengineers at the City College of New York (CCNY), showed that dually-targeted, antibody-guided nanoparticles, loaded with an existing chemotherapy drug, markedly improved tumor targeting, decreased tumor and metastatic growth and dramatically improved survival in a mouse model of triple-negative breast cancer. There were no observable side effects.

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How celastrol sensitizes brains to leptin, curbing hunger and obesity

celastrol path of action
Celastrol increases numbers of IL1R1 receptors in the brain, allowing leptin to act. (ILLUSTRATION: ELLA MARU STUDIO)

Here’s what’s known about celastrol, widely hailed in 2015 for its potent anti-obesity effects. It’s derived from the roots of the thunder god vine. It increases the brain’s sensitivity to leptin, the hormone that signals we’ve had enough to eat. It has curbed food intake by nearly 80 percent in obese mice, producing up to a 45 percent weight loss. It’s now in Phase 1 clinical trials conducted by ERX Pharmaceuticals; phase 2 studies are slated to begin this year.

What hasn’t been known is how celastrol makes the brain more sensitive to leptin. A study in today’s Nature Medicine finally provides an answer.

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50-year-old mystery solved — with clues to making more red blood cells

why steroids boost red blood cell production
Red blood cells produced by a single progenitor cell (IMAGE COURTESY HOJUN LI / DANA-FARBER/BOSTON CHILDREN’S VIA CELL PRESS)

Back in the 1950s, doctors began using steroids to treat Diamond-Blackfan anemia, or DBA, a severe condition in which patients cannot make enough red blood cells. There was no real rationale for using steroids, but there was no other good option, aside from regular transfusions. At the time, steroids were being thrown at seemingly everything.

But steroids worked in most patients, at least for a time — at the expense of serious side effects such as weight gain, bone loss, hypertension, diabetes and an increased risk of infections. A new study published yesterday in Developmental Cell finally explains why steroids work — and could provide a foothold for developing safer and better treatments for DBA. It could even pave the way to treatments for other types of bone marrow failure.

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Light-activated nanoparticles could avoid painful eye injections for ‘wet’ macular degeneration

Could intravitreal injections become a thing of the past?
(PHOTO: ZKALILA1998 / WIKIMEDIA COMMONS)

There are two standard treatments for “wet” age-related macular degeneration (AMD), in which abnormal, leaky blood vessels in the back of the eye lead to fluid buildup and vision loss. The first, injection of medication directly into the eye, can be painful and can cause inflammation, infection and detachment of the retina. The second, ablation therapy, uses lasers to destroy the leaky blood vessels. It, too, is unpleasant to undergo, and the lasers can also destroy surrounding healthy tissue, causing further vision loss.

In today’s Nature Communications, the lab of Daniel Kohane, MD, PhD, provides proof-of-concept of a more tolerable alternative: tiny, drug-carrying nanoparticles that can be injected intravenously, but deliver medication only to the eye.

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How the antidepressant ketamine rapidly awakens the brain, and why its effects vary more in women

(CREDIT: NATHALIE PICARD / BOSTON CHILDREN’S HOSPITAL)

In small doses, the anesthetic ketamine is a mildly hallucinogenic party drug known as “Special K.” In even smaller doses, ketamine relieves depression — abruptly and sometimes dramatically, steering some people away from suicidal thoughts. Studies indicate that ketamine works in 60 to 70 percent of people not helped by slower-acting SSRIs, the usual drugs for depression.

Two ketamine-like drugs are in the clinical pipeline, and, as of this week, one appears close to FDA approval. With no significant new antidepressant in more than 30 years, anticipation is high. Yet no one has pinned down how low-dose ketamine works. Studies have implicated various brain neurotransmitters and their receptors — serotonin, dopamine, glutamate, GABA receptors, opioid receptors — but findings have been contradictory.

“We felt it was time to figure this out once and for all,” says neuroscientist Takao Hensch, PhD.

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Blood stem cell transplants from any donor, without toxicity?

could stem cell transplants be made nontoxic?
(ADOBE STOCK)

Many blood disorders, immune disorders and metabolic disorders can be cured with a transplant of hematopoietic (blood-forming) stem cells, also known as bone marrow transplant. But patients must first receive high-dose, whole-body chemotherapy and/or radiation to deplete their own defective stem cells, providing space for the donor cells to engraft. These “conditioning” regimens are highly toxic: they wipe out the immune system, raising infection risk, and can cause anemia, infertility, other organ damage and cancers. And when the donor isn’t an exact match, patients’ immune systems must be suppressed for prolonged periods to prevent rejection.

As a result, most patients either don’t receive a transplant or must endure serious side effects. But if two new studies bear out in clinical trials, a far gentler conditioning treatment could enable stem-cell transplants for a much wider range of disorders, even possibly from unmatched donors.

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Can we mass-produce platelets in the lab?

Lab-grown platelets could someday be given to patients
Activated platelets (IMAGE: ADOBE STOCK)

Most of us have somewhere around a trillion tiny platelets zooming around our bloodstreams. Joseph Italiano, PhD, of Boston Children’s Hospital’s Vascular Biology Program, calls them the “Swiss Army knives of the blood.” In addition to their key role in clotting, platelets are important in immunity, wound healing, chemical delivery, blood vessel development and more.

At healthcare facilities, platelets are in constant demand for patients with blood diseases, or those receiving radiation or chemotherapy for cancer. But unlike other blood products, platelets can’t be stored for more than a few days. If there’s a snowstorm or other emergency preventing donors from giving platelets, a hospital can easily run out. So researchers have been trying to make platelets in a lab setting.

Two teams at Boston Children’s Hospital are tackling the problem in slightly different ways.

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Natural killer cells: A new angle on neuropathic pain

natural killer cells, peripheral nerve damage and neuropathic pain
Like an immune cleanup crew, natural killer cells (green) infiltrate a damaged axon. (IMAGE: ALEXANDER DAVIES / SEOUL NATIONAL UNIVERSITY AND UNIVERSITY OF OXFORD)

Scientists have known since the 1800s what happens to a totally crushed peripheral nerve in animals: the damaged axons are broken down in a process called Wallerian degeneration, allowing healthy ones to regrow. But humans rarely suffer complete axonal damage. Instead, axons tend to be partially damaged, causing neuropathic pain — a difficult-to-treat, chronic pain associated with nerve trauma, chemotherapy and diabetes.

The lab of Michael Costigan, PhD, in Boston Children’s Hospital’s F.M. Kirby Neurobiology Center is studying how the body’s immune system breaks down these damaged nerves. Their latest research, published today in Cell, may change our understanding of neuropathic pain and how to treat it.

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Drug repurposing and DNA mining: The hunt for new endometriosis treatments

endometriosis researchers Michael Rogers and Danielle Peterse
Michael Rogers and Daniëlle Peterse (PHOTO: MICHAEL GODERRE/BOSTON CHILDREN’S HOSPITAL)

Endometriosis is a common gynecological condition that may affect more than 1 in 10 reproductive-age women. Yet, there’s very little research into the disease and limited options for treatment. A team in the Vascular Biology Program at Boston Children’s Hospital is trying to change that.

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Overriding resistance to epigenetic inhibitors in neuroblastoma: Targeting PI3K

(IMAGE COURTESY NATIONAL CANCER INSTITUTE)

Children’s cancers pose unique challenges. They’re not caused by the same kinds of genetic mutations that cause adult cancers, and only a minority of their mutations can be targeted with drugs. In a recent study, Kimberly Stegmaier, MD, at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and her colleagues systematically deleted every gene in the genome in a number of childhood cancers. This led them to previously unknown — and targetable — genes that help drive tumor growth.

But Stegmaier is also interested in epigenetic regulators — proteins that help control the regulation of genes and contribute to many pediatric cancers. They’re a hot subject of research: Child cancers tend to arise in developing tissues, and epigenetic regulators are active during early development. Clinical trials are starting to test drugs that inhibit epigenetic cancer-promoting factors.

There’s a problem, though: Cancers often become resistant to targeted inhibitors, including epigenetic inhibitors. So, again using genome-wide approaches, Stegmaier set out to find ways to overcome this resistance.

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