Among all cancers, brain cancer remains among the most difficult to treat. But there are new, promising treatments in the pipeline.
“Brain cancers are catastrophic diseases,” said Ely Benaim, M.D., Chief Medical Officer of SonALAsense (pictured above), an innovative biotech company founded to provide a non-invasive way to treat brain cancer as well as other difficult-to-treat cancers.
“Cancers of the brain are conditions with virtually no effective therapies. But we are working to change this and make a difference in these patients’ lives,” Benaim told Breaking Cancer News.
Founded in 2019, SonALAsense is focused on providing hope in the face of despair by developing sonodynamic therapy (SDT) into a safe, effective treatment for brain cancer and other cancers.
SDT is a nonsurgical drug-device combination that takes advantage of cancers’ hunger to create smart bombs from their drug, SONALA-001. The drug, coupled with focused ultrasound, selectively kill tumor cells, said Stuart Marcus, MD, PhD, SonALAsense co-founder and Chief Science Officer.
He added that cells need an amino acid called 5-aminolevulinic acid (ALA) to produce heme, which is essential for cellular energy production.
“If you give normal cells too much ALA, they just ignore it. But cancer cells will just keep accumulating it, which disrupts their heme metabolism at a key point in the process and that creates a vulnerability we can use to kill them,” Marcus said.
A New Way to Kill Cancer
According to the Mayo Clinic, photodynamic therapy (PDT) is a two-stage treatment that combines light energy with a drug (photosensitizer) designed to destroy cancerous and precancerous cells after light activation.
Photosensitizers are activated by a specific wavelength of light energy, usually from a laser. Flooding tumor cells with ALA causes accumulation of protoporphyrin, Marcus explained, which fluoresces pink when exposed to low energy light, and when exposed to higher energy light produces reactive oxygen molecules that destroy cancer cells.
Photodynamic therapy energizes protoporphyrin with light to destroy skin carcinomas and pre-cancers. Protoporphyrin’s fluorescent properties have been used by neurosurgeons to visualize and remove glioblastoma (GBM).
In 2012, researchers showed that sound energy could activate protoporphyrin, generate reactive oxygen and destroy cancer cells. Marcus and colleagues leveraged these findings to develop SDT.
Getting This Treatment to Patients As Soon As Possible
Benaim will work to accelerate this process to get SDT rapidly to patients. He will lead clinical operations, data management, and safety, and play a major role in regulatory filings. He will also be an ambassador for the company, sharing information about this novel therapy with the oncology community.
“We’re creating a new treatment path that steers away from invasive and toxic therapies that cause patients to suffer even more than the illness they are diagnosed with,” said Benaim.
“We believe our incisionless approach with SDT has great potential to destroy cancer without the many side effects associated with current therapies.”
Mitchel Berger, MD, Professor of Neurological Surgery, University of California, San Francisco and Director of UCSF’s Brain Tumor Center, recently said on the SonALAsense website that this method “could convert recurrent GBM from a lethal disease to a manageable chronic illness.”
How Sonodynamic Therapy Works
During SDT, a form of ALA, SonALAsense’s SONALA-001 drug is given intravenously. A few hours later, the patient is exposed to MRI-guided focused ultrasound to activate the protoporphyrin.
After treatment, patients can remarkably walk out of the hospital as if this was a simple outpatient procedure and go about the rest of their day, maintaining their quality of life.
Because normal cells can manage excess ALA, SonALAsense scientists believe SDT can effectively kill cancer cells without the collateral damage associated with chemotherapy, radiation, surgery and other treatments.
In addition, because SDT attacks a basic cellular function, tumors should have difficulty escaping treatment or developing resistance to SDT.
“Sonodynamic therapy targets the cell’s energy metabolism, not a mutation or some tumor trait that blinds a patient’s immune system,” said Marcus. “Cancer cells can develop escape mutations that protect them from targeted therapies, but it would be incredibly difficult for them to completely change their basic energy-producing metabolism.”
The Most Common Types of Brain Cancer:
These are the most common types of brain tumors that are categorized by the types of cells of which they are made up, according to The Preston Robert Tisch Brain Tumor Center:
- Glioma: A tumor that originates from glial cells;
- Astrocytoma: A type of glioma that includes glioblastomas, the fastest-growing type of tumor in the brain;
- Meningioma: A tumor that grows in the tissue surrounding the brain and spinal cord. It is the most common type of brain tumor in adults and aretypically benign and slow-growing;
- Ganglioglioma: A slow-growing tumor that is found in glial cells and neurons;
- Craniopharyngiomas: A slow-growing tumor that forms between the pituitary gland and the brain. It often presses on optic nerves, resulting in vision difficulties;
- Medulloblastoma: A fast-growing tumor that forms on the brain’s nerve cells and is more commonly found in children.
Early-Stage Trials
SonALAsense is the first company to test sonodynamic therapy in human trials, having launched a phase 1b clinical trial for children with diffuse intrinsic pontine glioma (DIPG), a very aggressive type of brain cancer.
This occurs in an area of the brainstem (the lowest, stem-like part of the brain) called the pons, which controls many of the body’s most vital functions such as breathing, blood pressure, and heart rate.
Supported by a $2 million National Cancer Institute grant, the trial is measuring SDT safety, tumor size reductions and patient performance.
In 2021, a phase 0/1 trial was conducted at the Ivy Brain Tumor Center in Phoenix, Arizona for recurrent glioblastoma.
In this study, although the patients received SONALA-001, reaching the whole tumor, the SDT was given to only half of the tumor before surgery allowing to evaluate this therapy in the same patient.
The researchers found SDT induced tumor cell death with no significant safety issues. These promising results led to an ongoing phase 2 trial.
“Preclinical studies and early-stage trials have all been quite promising,” said Mark de Souza, PhD, Chief Executive Officer at SonALAsense.
“We are excited by the prospect that we can bring hope to patients who have been waiting so long for a way to make cancer a manageable disease and improve quality of life.”
Benaim began his career as a pediatric oncologist at St. Jude Children’s Research Hospital. Later, he moved into drug development, taking high-profile positions at Amgen, Sangamo BioSciences, Millennium Pharmaceuticals, Rexahn Pharmaceuticals and others.
Focused and Optimistic
Prior to joining SonALAsense, Benaim was Chief Medical Officer for Novocure, where he managed several pivotal clinical trials.
“I’ve always been attracted to challenging conditions, such as orphan diseases, and driven to accelerate approvals because there were no therapies,” said Benaim.
“When people say something cannot be done, that’s when I really start getting interested. Both DIPG and glioblastoma are incredibly challenging conditions, and I wanted to be part of the solution.”
While these studies are in the early stage, researchers are hopeful that this approach can extend survival and improve quality of life for GBM and DIPG patients.
In addition, SonALAsense executives believe SDT could treat multiple tumor types, including pancreatic, ovarian, bladder, lung and breast, without surgery or toxic chemicals.
It may sound too good to be true, but the technology is showing some promise. This is a company to watch.
