Research & Development

5–Aminolevulunic Acid (5-ALA)

5-ALA – Naturally occurring amino acid

5-ALA stands for 5-aminolevulinic acid, a type of amino acid which is produced universally by life forms such as plants and animals. In the human body, 5-ALA is a component of a substance called heme which is formed by a combination of eight 5-ALA molecules and is key to a number of vital functions.

A familiar function of heme is the formation of red pigment (hemoglobin) in the blood, which distributes oxygen throughout the body. Oxygen and heme combine or separate, depending on the surrounding environment, and oxygen is delivered from the lungs throughout the entire body. In addition, heme is the central substance in the respiratory chain complex that produces energy from food and oxygen, which is the basis of our vital functions. Without 5-ALA we would not be able to gain energy or even move.

Chlorophyll, which plays a central role in plant photosynthesis, is also formed by combining eight 5-ALA molecules, and its structure is very close to heme. Plants produce oxygen and cells by photosynthesis using light and carbon dioxide. Animals, including humans, consume oxygen and plants and exhale carbon dioxide and plants grow again using that same carbon dioxide. This is the energy cycle of life and it cannot be achieved without its two axes—heme and chlorophyll— both of which are formed from 5-ALA.

 5-ALA – Ingestion

In many cases, simply ingesting a substance that originally exists in the body will not reach its place of origin or the place where its effects are needed. However, this isn’t the case for 5-ALA, as oral ingestion allows it to exert its original function AND change into heme.

This is possible because firstly, 5-ALA is created in mitochondria, tiny organs (organelles) inside the cell, but is then immediately expelled from the mitochondria. After being assembled almost into its final form outside the mitochondria, it is then reintroduced into the mitochondria before bonding with iron (iron atoms) to complete the heme production (see diagram).

Secondly it is due to the size of 5-ALA. In general, water-soluble substances like 5-ALA cannot pass through cells, but 5-ALA’s structure and size is similar to dipeptide, a two-amino-acid chain produced during the breakdown of protein (food) and can pass through cells using a gate (called a transporter) for dipeptides on the cell surface.

Therefore orally ingested 5-ALA and 5-ALA naturally produced in the body are combined inside the cell/outside the mitochondria and together form heme.

5-ALA – Accumulation of Protoporphyrin IX (PpIX)

The synthesis of 5-ALA is regulated by an intracellular pool of free heme through a negative feedback mechanism. Administration of an excess of exogenous 5-ALA bypasses the negative feedback control, resulting in selective accumulation of protoporhyrin IX (PpIX) in tumor cells such as malignant gliomas or actinic keratoses.

Formation of PpIX from 5-ALA

PpIX serves as a so-called photosensitizer, which is illuminated with light of an appropriate wavelength.

The fluorescence property of PpIX is used in fluorescence diagnostics for visualization of malignant gliomas (WHO grade III-IV). Here, the violet-blue illumination of PpIX (λ =400-410 nm) results in bright red-pink fluorescence in tumor tissue, which can be more accurately removed compared to blue-appearing normal tissue. The use of special filter technologies in neurosurgical operating microscopes makes this fluorescence-assisted surgery possible.

Due to the increased penetration depth of red light (λ =635 nm) compared to light with shorter wavelengths, red light is used for photodynamic therapy (PDT). Excitation of PPIX with red light results in the formation of reactive oxygen species. These species, mainly singlet oxygen, damage the target cells and eventually lead to cell death.

5-ALA Trials

There are a number of trials, some of which are currently recruiting patients. Please click on the trials highlighted below to be taken to the relevant information.

Compound Indications Territory Study Identifier Recruiting Status
5-ALA FGS – Ovarian Cancer US NCT05804370 Recruiting
5-ALA Diagnostic – Colorectal Cancer EU 2023-508668-31-00 Recruiting
5-ALA PDT – Glioblastoma EU NCT03897491 Completed

FGS – Fluorescence Guided Surgery   |   PDT – Photodynamic Therapy

Investigator Initiated Trials (IITs)

IITs are investigator-conceived studies that complement our current research collaborations. We are committed to providing researchers with the opportunity to explore innovative ideas and address unmet medical needs, with the ultimate goal of improving patient outcomes.

All submissions are evaluated by a dedicated medical and scientific committee to ensure scientific excellence and alignment with photonamic’s research priorities. Through a structured process, each study is thoroughly assessed, operationally prepared, and ethically sound before initiation.

Study Title Sponsor Study Identifier Recruiting Status
5-Aminolevulinic Acid (5-ALA) for Intraoperative Imaging in Patients with Ovarian Cancer – a Single Center Feasibility Study (ILLUMINATE) Rheinische Friedrich-Wilhelms-Universitaet Bonn 2024-510614-33-00 Recruiting

Phase I/II dose escalation trial of radiodynamic therapy (RDT) with 5-Aminolevulinic acid in patients with first recurrence of glioblastoma

Westfälische Wilhelms-Universität Münster, Schlossplatz 2, 48149 Münster NCT05590689 Recruiting

Clinical safety study on 5-Aminolevulinic acid (5-ALA) in children and adolescents with supratentorial brain tumors

Westfälische Wilhelms-Universität Münster, Schlossplatz 2, 48149 Münster NCT04738162
Enquiry Form

If you are interested in 5-ALA and want to collaborate or partner with us, please get in touch.

photonamic GmbH & Co. KG

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Enquiry Form

Enquiry Form

If you are interested in 5-ALA and want to collaborate or partner with us, please get in touch.

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